Food Insecurity and Intimate Partner Violence in Mwanza, Tanzania: A Longitudinal Analysis.
Food insecurity is a potential predictor of intimate partner violence. This study (1) describes the prevalence of food insecurity and various forms of intimate partner violence experience among women in Mwanza, Tanzania; and (2) assesses the effect of food insecurity and hunger on various forms of women's experience of intimate partner violence longitudinally. Women (aged 18-70 years) who reported being in a relationship in the past 12 months, who had participated in the control arms of two randomized controlled trials conducted as part of the MAISHA study were interviewed at four time points (N=1,004 at baseline in 2017). Analyses were conducted in 2022. Associations between food insecurity exposures and intimate partner violence outcomes were assessed, and univariate random effect logistic models were conducted to identify relevant sociodemographic variables (including age, education level, and SES) that were statistically significant. Multivariable random effects logistic models were conducted, including time as a fixed effect, to calculate odds ratios indicating associations between food insecurity exposures and intimate partner violence outcomes. Prevalence of food insecurity was 47.7%, 55.6%, 47.2%, and 50.8% for each of the 4 waves, respectively, with significant difference in proportion of food insecurity between baseline and Wave 2. Multivariable random effects models indicated that food insecurity was associated with increased odds of exposure to all forms of intimate partner violence outcomes, and hunger was significantly associated with increased odds of experience of all intimate partner violence outcomes, apart from controlling behaviors. Results from this longitudinal analysis of food insecurity and women's reports of intimate partner violence experience in a low- and middle-income country setting indicate that food insecurity is significantly associated with all forms of intimate partner violence, apart from controlling behaviors, among women in this sample in Mwanza, Tanzania. Policy and programmatic implications include the need for integrated intimate partner violence prevention programming to take into account household food needs.


Selective facilitation of memory attributes by strychnine.
In two experiments, the effects of strychnine on the specific memory attributes of prior discrimination training were assessed in terms of subjects' performance under various discrimination reversal conditions. Mice were trained in a discrimination task with two redundant relevant cues. Immediately after their last training trial, subjects were administered an intraperitoneal injection of either strychnine (1.0 mg/kg) or saline. When both training cues were reversed (Experiment 1), strychnine treated subjects were observed to exhibit greater performance decrements than saline-treated subjects upon initial exposure to reversal conditions, suggesting that strychnine had enhanced the memory of a relatively specific stimulus-response association. When subjects were tested under partial cue-reveraal conditions (Experiment 2) strychnine treated animals exhibited treater utilization of one of the redundant relevant stimuli than the other, while saline-treated animals exhibited no preference.


Bilateral temporomandibular joint dislocation with locked mandibular impaction.
Bilateral anterior temporomandibular joint dislocation is very rare, with only 2 reported cases published. In the present report, we describe a healthy 25-year-old man from Haida Gwaii, in British Columbia, Canada, who was transferred to our tertiary trauma center with life-threatening complications of a bilateral anterior temporomandibular joint dislocation with locked mandibular impaction.


Effect of 1,25-dihydroxyvitamin D3 on phospholipid metabolism in chick duodenal mucosal cell. Relationship to its mechanism of action.
Pretreatment of the D-deficient chick with 1,25-dihydroxyvitamin D3 increases de novo synthesis of phosphatidylcholine by a stimulation of CDP-choline: sn-1,2-diacylglycerol choline-phosphotransferase reaction. The time course of change in the incorporation of [3H]choline and [14C]ethanolamine into the brush border lipid fraction after 1,25-dihydroxyvitamin D3 treatment correlates closely with the time course of change in calcium uptake into the brush border membrane vesicles. Prior treatment with cycloheximide does not block this increase in phosphatidylcholine synthesis. In addition, 1,25-dihydroxyvitamin D3 administration increases the incorporation of [3H]arachidonic acid into the phosphatidylcholine fraction of the brush border to a great extent but does not increase the incorporation of [3H]palmitic acid into the phosphatidylcholine fraction. The incorporation of these 3H labeled fatty acids into diacylglycerol is not changed by 1,25-dihydroxyvitamin D3. These data indicate that 1,25-dihydroxyvitamin D3 enhances the synthesis of phosphatidylcholine independent of new protein synthesis, and also increases the incorporation of unsaturated fatty acids into phosphatidylcholine. From these results we suggest that changes in phospholipid metabolism in the enterocyte are the mechanisms by which 1,25-dihydroxyvitamin D3 acts to enhance calcium entry across the brush border membrane.


Mortality and light to moderate alcohol consumption after myocardial infarction.
Although heavy alcohol consumption increases total mortality, light to moderate consumption decreases cardiovascular and all-cause mortality in apparently healthy people. Since data are sparse on the relation of light to moderate alcohol intake to mortality in patients with previous myocardial infarction, we did a prospective study of mortality in men. Of 90,150 men in the Physicians' Health Study enrollment cohort who provided information on alcohol intake and who had no history of cancer, stroke, or liver disease, 5358 had a previous myocardial infarction. We estimated alcohol consumption by food-frequency questionnaire. During a mean follow-up of 5 years, 920 men died. After adjustment for several potential confounders, moderate alcohol intake was associated with a significant decrease in total mortality (p=0.016). Compared with men who rarely or never drank alcohol, those who drank one to four drinks per month had a relative risk for total mortality of 0.85 (95% CI 0.69-1.05); for two to four drinks per week, the relative risk was 0.72 (0.58-0.89); for one drink per day 0.79 (0.64-9.96); and for two or more drinks per day 0.84 (0.55-1.26). Men with previous myocardial infarction who consume small to moderate amounts of alcohol have a lower total mortality.


Aspirin intolerance and the need for dual antiplatelet therapy after stent implantation: a proposed alternative regimen.
Dual antiplatelet therapy (DAT, i.e. aspirin+thienopyridine) has been shown to reduce the risk of stent thrombosis (ST) and myocardial infarction (MI) after coronary stent implantation. Data regarding alternative antiplatelet therapy in patients with allergy or intolerance to aspirin are lacking. This study is a retrospective analysis of consecutive patients with adverse reactions to aspirin who received an alternative combination of DAT (indobufen, trapidil, or triflusal in association with a thienopyridine) after elective implantation of either drug-eluting (DES) or bare-metal stents (BMS). Endpoints analyzed were cardiac death, MI, ST and bleeding. A total of 127 patients undergoing stenting of 267 lesions (DES 84%, BMS 16%), were identified between June'99 and November'08. Reasons for not taking aspirin included gastrointestinal intolerance (53.5%), allergy (39.4%), non-gastrointestinal bleeding (5.5%) and others (1.6%). Aspirin was substituted with indobufen (64.6%), trapidil (26.8%), triflusal (6.3%), or a combination of indobufen+trapidil (2.4%). Median duration of DAT was 369 days [IQR 273-1053] after DES and 46.5 days [IQR 30-699] after BMS implantation. Only 3.1% of patients prematurely discontinued DAT. During a median follow-up of 1161 days [IQR 781-1538], rates of cardiac death and MI were 3.1% and minor bleeding occurred in 1.5%. There was 1 very late definite ST occurring 2 days after DAT discontinuation and no probable ST. In this cohort of patients with aspirin intolerance undergoing coronary stent implantation, the combination of a thienopyridine with indobufen, trapidil, or triflusal was associated with a low rate of cardiac death, ST and MI.


Aberrant expression and possible involvement of the leptin receptor in endometrial cancer.
Leptin and its receptor are the key players in the regulation of energy balance and body weight control. However, their roles in gynecological malignancies are mostly unclear. In this study, we analyzed the expression and possible involvement of leptin and the leptin receptor in the pathogenesis of endometrial cancer. Radioimmunoassay was performed to analyze the serum leptin levels in the endometrial cancer patients, while RT-PCR, immunoblotting, and immunohistochemistry techniques were applied to study the expression of leptin receptor in the endometrioid-type endometrial cancer tissues. Furthermore, BrdU labeling followed by immunofluorescent analysis was used to analyze the effect of leptin receptor overexpression on endometrial cancer cell proliferation. Serum leptin levels are elevated in endometrial cancer patients, but show no significant difference to those of normal controls when normalized by body mass index. On the other hand, lower expression levels of leptin receptor short form (Ob-Ra) were observed in most endometrial cancer tissues, especially in the poorly differentiated ones, and the forced expression of Ob-Ra in RL95-2 endometrial cancer cells prevented them from entering the S-phase. In summary, our data demonstrates for the first time that the leptin receptor is aberrantly expressed in endometrial cancer tissues and is possibly involved in the pathogenesis of endometrial cancer.


Inferences on the potential effects of presumed nondifferential exposure misclassification.
In the presentation and discussion of epidemiologic study results, investigators often argue that their results have to be viewed as conservative due to the occurrence of presumedly nondifferential exposure misclassification. Sometimes attempts are made to correct for this supposed bias toward the null. Particularly, various dual exposure measurement strategies that may eliminate or at least reduce the bias if the exposure misclassification is truly nondifferential have gained much popularity in recent years. However, even in cohort studies, it is often questionable whether the exposure misclassification rates are completely independent of measured disease risk. In this article, I assess the effects of violating the assumption of nondifferential misclassification on the direction and magnitude of bias and on the misclassification correction procedures. Even slight violation of the nondifferentiality assumption can lead to large bias away from the null or to crossover bias, particularly if dual measurement procedures are used to correct for exposure misclassification. Consequently, inferences on the potential effects of presumedly nondifferential exposure misclassification in any given study should only be made after careful sensitivity analyses that take into account the full range of plausible misclassification rates as well as of plausible deviations from nondifferentiality.


Private health insurance, mental health and service use in Australia.
To report on the private health insurance (PHI) status of individuals with and without a mental health problem, and examine whether PHI status is associated with access to psychological services. This is a descriptive study of nationally representative population-based data collected in 2009 (HILDA) with participants aged 15-93 (n = 13,301). Key measures included: PHI status (categorised as 'hospital cover only', 'extras cover only', or 'both hospital and extras cover'); mental health status (categorised as 'have a mental health problem' or 'do not have a mental health problem' using the mental health index (MHI) of the medical outcomes study short form); mental health service use (access to a mental health professional (psychologist/psychiatrist) in the past 12 months categorised as 'yes' or 'no'). Individuals with a mental health problem were less likely to have PHI than those without a mental health problem. However, PHI was not associated with access to a mental health professional in the past 12 months. The findings suggest that while the discrepancy in PHI status is a marker of inequity between those with and without a mental health problem, it is not a key factor in facilitating access to mental health services.


Vertical mammaplasty for gigantomastia.
A 48-year-old female patient presented with gigantomastia. The sternal notch-nipple distance was 55 cm for the right breast and 50 cm for the left. Vertical mammaplasty based on the superior pedicle was performed. The resected tissue weighed 3400 g for the right breast and 2800 g for the left breast. The outcome was excellent with respect to symmetry, shape, size, residual scars, and sensitivity of the nipple-areola complex. Longer pedicles or larger resections were not found in the literature on vertical mammaplasty applications. In our opinion, by using the vertical mammaplasty technique in gigantomastia it is possible to achieve a well-projecting shape and preserve NAC sensitivity.


Plant biodiversity and carbon sequestration potential of the planted forest in Brahmaputra flood plains.
Globally, while experts debated whether planted forests (PF) restore biodiversity or create biological deserts, their potential role in mitigating climate change is mostly overlooked. In this study, we investigated the long-term impact of PF on the species composition, plant diversity, biomass stock, and carbon (C) storage potential in the Brahmaputra flood plain of North-East India. The phytosociological study was conducted using a modified Gentry plot method and species-specific allometric models were used to estimate biomass stock in the 39-year old PF and equivalent age of natural forest (NF). We identified 57 trees, 22 shrubs, and 23 herb species in the PF, and 54 trees, 17 shrubs, and 8 herb species in the NF. Species richness and biodiversity indices showed greater values in PF whereas species dominance and evenness were higher in NF. After 39-year of plantation, total biomass C was estimated at 165 Mg C ha-1 in PF and 197 Mg C ha-1 in equivalent age of NF. Bombax ceiba, Dalbergia sissoo, Samanea saman, Tetrameles nodiflora, and Gmelina arborea were the dominant tree species that contribute 56% of the total biomass C in the PF. The ecosystem carbon pool (plant biomass + deadwood + litter + SOC) was 17% higher in NF and showed the greater potential of carbon dioxide sequestration (959 Mg CO2 ha-1) compared to the PF (818 Mg CO2 ha-1). Our study suggested PF in flood plain degraded lands can act as a major C sink and stored a substantial amount of carbon dioxide after 39-year of the plantation. It is concluded that PF can be a preferable ecosystem management tool to fulfill the objectives of biodiversity conservation and provisioning climate services like C sequestration.


Rare mucocutaneous manifestations of ulcerative colitis: A case report of pyostomatitis vegetans and Sweet syndrome.
Inflammatory bowel diseases (IBD) are chronic inflammatory disorders of the digestive tract, and they involve systemic inflammatory diseases known as extra-intestinal manifestations (EIMs). Timely and correct diagnosis of mucocutaneous EIMs could assist with detecting and monitoring IBD. We present a case of 52-year-old male patient of ulcerative colitis with 2 rare EMIs together at the same time: pyostomatitis vegetans in the oral cavity and Sweet syndrome on the skin. They presented as multiple small white or yellow pustules on the surface of the hyperemic fragile oral mucosa and abrupt appearance of painful, swollen, and erythematous papules on the skin, respectively. The final diagnosis was made based on clinical manifestations, skin and oral tissue biopsies, and the ulcerative colitis history. This rare case report may remind dentists of rare mucocutaneous EIMs of IBD that might be overlooked. Dentists and dermatologists could contribute to the early diagnosis and management of systematic diseases.


Characteristics of Micro/Nano Pores and Hydrocarbon Accumulation in a Continental Shale Oil Reservoir-A Case Study of the Lucaogou Formation in the Jimsar Sag, Junggar Basin, Northwest China.
This paper comprehensively studies the micro- and nanometer-scale pore characteristics and structure of the Lucaogou Formation shale oil reservoir in the Jimsar Sag using high-pressure mercury analysis, field emission scanning electron microscopy and nano-CT scanning technology. In addition, the occurrence states of crude oil in pores are analyzed combined with macro-micro characteristics. The results show that there are various reservoir types; the main reservoir pore structure is on the micron and nanometer levels, with other void spaces including intergranular pores, interparticle dissolution pores, intercrystalline pores and microfissures. Nanopores are generally oil-bearing and mostly in the adsorption state, which changes the traditional understanding that micron pores are the only microscopic pores in the reservoir and confirms that shale oil exists in 'sweet spots' and mud-shale sections of the Lucaogou Formation.


Functional characterization of Asp-317 mutant of human renin expressed in COS cells.
Renin is an unique aspartyl (acid) protease with optimal activity at neutral pH. It has been suggested that Ala-317 of human renin contributes to neutral optimum pH of the enzyme [(1984) FEBS Lett. 174, 102-111]. The hypothesis was verified by the characterization of mutant renin in which Ala-317 was replaced with Asp by a site-directed mutagenesis. Wild-type and mutant renins, which were expressed in COS cells, exhibited different pH-activity profiles and optimum pH of the mutant enzyme was lower than that of the wild-type enzyme. This result suggests that Ala-317 of human renin plays an important role in the determination of optimum pH of the enzyme.


Calnuc-derived nesfatin-1-like peptide is an activator of tumor cell proliferation and migration.
Calnuc (nucleobindin-1, nucb1) is a Ca2+ -binding protein involved in the etiology of many human diseases. To understand the functions of calnuc, we have identified a nesfatin-1-like peptide (NLP) in its N terminus that is proteolyzed by a convertase enzyme in the secretory granules of cells. Mutational studies confirm the presence of a proteolytic cleavage site for proprotein convertase subtilisin/kexin type 1 (PCSK1). We demonstrate that NLP regulates Gαq-mediated intracellular Ca2+ dynamics, likely via a G-protein-coupled receptor. NLP treatment to carcinoma cell lines (SCC131 cells) promotes the expression of regulators of cell cycle, proliferation, and clonogenicity by the AKT/mTOR pathway. NLP is causative of augmented migration and epithelial-mesenchymal transition (EMT), illustrating its metastatic propensity and establishing its tumor promotion ability.


Dental students' attitude to gender roles.
This investigation assessed attitudes held by United States women and men dental students toward professional and sex role concepts. The concepts included: female dental student, male dental student, dentist, adult woman, adult man, wife and husband. These attitudes were evaluated and compared in the context of the students' current and future professional roles and their sex roles. Although there were several differences in attitudes between the two subject groups, the results suggest that the women and men dental students viewed their various roles as consistent with one another. It is particularly important to note that the women dental student is viewed by both gender groups as having professional and sex roles which do not conflict.


Translational implications of newly characterized pathogenic pathways in systemic lupus erythematosus.
Improved characterization of relevant pathogenic pathways in systemic lupus erythematosus (SLE) has been further delineated over the last decades. This led to the development of targeted treatments including belimumab and anifrolumab, which recently became available in clinics. Therapeutic targets in SLE encompass interferon (IFN) signaling, B-T costimulation including immune checkpoints, and increasing modalities of B lineage targeting, such as chimeric antigen receptor (CAR) T cells directed against CD19 or sequential anti-B cell targeting. Patient profiling based on characterization of underlying molecular abnormalities, often performed through comprehensive omics analyses, has recently been shown to better predict patients' treatment responses and also holds promise to unravel key molecular mechanisms driving SLE. SLE carries two key signatures, namely the IFN and B lineage/plasma cell signatures. Recent advances in SLE treatments clearly indicate that targeting innate and adaptive immunity is successful in such a complex autoimmune disease. Although those signatures may interact at the molecular level and provide the basis for the first selective treatments in SLE, it remains to be clarified whether these distinct treatments show different treatment responses among certain patient subsets. In fact, notwithstanding the remarkable amount of novel clues for innovative SLE treatment, harmonization of big data within tailored treatment strategies will be instrumental to better understand and treat this challenging autoimmune disorder. This review will provide an overview of recent improvements in SLE pathogenesis, related insights by analyses of big data and machine learning as well as technical improvements in conducting clinical trials with the ultimate goal that translational research results in improved patient outcomes.


Stabilization of charges on isolated ionic groups sequestered in proteins by polarized peptide units.
Electrostatic interactions are of considerable importance in protein structure and function, and in a variety of cellular and biochemical processes. Here we report three similar findings from highly refined atomic structures of periplasmic binding proteins. Hydrogen bonds, acting primarily through backbone peptide units, are mainly responsible for the involvement of the positively charged arginine 151 residue in the ligand site of the arabinose-binding protein, for the association between teh sulphate-binding protein and the completely buried sulphate dianion, and for the formation of the complex of the leucine/isoleucine/valine-binding protein with the leucine zwitterion. We propose a general mechanism in which the isolated charges on the various buried, desolvated ionic groups are stabilized by the polarized peptide units. This mechanism also has broad application to processes requiring binding of uncompensated ions and charged ligands and stabilization of enzyme reaction charged intermediates, as well as activation of catalytic residues.


Amphiregulin may be a new biomarker of classically activated macrophages.
Amphiregulin (Areg) participates in tissue repair and inflammation regulation. As important effector cells in inflammation, macrophages can be polarized to classically (M1) or alternatively (M2) activated phenotype with diverse functions in immunity. However, the relationship between Areg expression and macrophage activation is poorly understood. Here we report that Areg was significantly expressed in M1 but not in M2 macrophages. This was confirmed by analyses of RT-PCR and ELISA in peritoneal macrophages, and by evaluating protein expression in alveolar macrophages and RAW264.7 cells. Selective inhibitors of TLR4 (CLI-095) and MAP kinase, including Erk1/2 (PD98059), JNK (SP600125) and p38 (SB203580), significantly reduced Areg expression in M1 macrophages, suggesting that M1 macrophages produce Areg mainly through the TLR4-MAPK pathway, which is involved in the mechanism of M1 activation. When compared with productions of classical biomarkers of M1 macrophages, Areg expression was highly consistent in time series. Taken together, Areg may be an effective new biomarker of M1 macrophages.


The 5' → 3' exoribonuclease XRN1/Pacman and its functions in cellular processes and development.
XRN1 is a 5' → 3' processive exoribonuclease that degrades mRNAs after they have been decapped. It is highly conserved in all eukaryotes, including homologs in Drosophila melanogaster (Pacman), Caenorhabditis elegans (XRN1), and Saccharomyces cerevisiae (Xrn1p). As well as being a key enzyme in RNA turnover, XRN1 is involved in nonsense-mediated mRNA decay and degradation of mRNAs after they have been targeted by small interfering RNAs or microRNAs. The crystal structure of XRN1 can explain its processivity and also the selectivity of the enzyme for 5' monophosphorylated RNA. In eukaryotic cells, XRN1 is often found in particles known as processing bodies (P bodies) together with other proteins involved in the 5' → 3' degradation pathway, such as DCP2 and the helicase DHH1 (Me31B). Although XRN1 shows little specificity to particular 5' monophosphorylated RNAs in vitro, mutations in XRN1 in vivo have specific phenotypes suggesting that it specifically degrades a subset of RNAs. In Drosophila, mutations in the gene encoding the XRN1 homolog pacman result in defects in wound healing, epithelial closure and stem cell renewal in testes. We propose a model where specific mRNAs are targeted to XRN1 via specific binding of miRNAs and/or RNA-binding proteins to instability elements within the RNA. These guide the RNA to the 5' core degradation apparatus for controlled degradation.


Effect of indexed glomerular filtration rate according to age.
To find out up to what age there is dispersion in glomerular filtration rate (GFR) values when normalised by body surface area (BSA) and extracellular fluid volume (ECFV), based on the hypothesis that these values differ in childhood age. A retrospective study was performed on patients aged 0-85 years, with renal pathology, who were administered i.v. 51Cr-EDTA. GFR was obtained using the Ham and Piepsz (children) or Christensen and Groth (adults) formula. Results were normalised by BSA and ECFV. The cut-off point is defined as the age that discriminates between values ± 10 points apart. Using a ROC curve analysis, this age was set at 11.96 years with a sensitivity of 0.83 and a specificity of 0.85. The area obtained was 0.902 (95%CI 0.880-0.923). The results were corroborated by linear regression stratifying by age. For children under 12 years of age, the Pearson correlation was 0.883 (95% CI 0.860-0.902). For those aged 12 years or older, this coefficient was 0.963 (95%CI 0.957-0.968). According to our results, when normalising GFR by BSA and by ECFV there are different behaviours according to age. For children older than 12 years both normalisation methods can be used, but for children younger than 12 years there are differences. We believe that in children under 12 years of age, GFR should be normalised by ECFV.


Survey of noncortical afferent projections to the basilar pontine nuclei: a retrograde tracing study in the rat.
The retrograde transport of the conjugate wheat germ agglutinin-horseradish peroxidase (WGA-HRP) was used in the rat to identify the cell bodies of origin for all subcortical projections to the basilar pontine nuclei (BPN). A parapharyngeal surgical approach was used to allow the injection micropipette to enter the BPN from the ventral aspect of the brainstem and thus avoid any potential for false-positive labeling due to transection and injury-filling of axonal systems located dorsal to the basilar pontine gray. A surprisingly large number of BPN afferent cell groups were identified in the present study. Included were labeled somata in the lumbar spinal cord and a large variety of nuclei in the medulla, pons, and midbrain, as well as labeled cells in diencephalic and telencephalic nuclei such as the zona incerta, ventral lateral geniculate, hypothalamus, amygdala, nucleus basalis of Meynert, and the horizontal nucleus of the diagonal band of Broca. Quite a number of cell groups known to project directly to the cerebellum also exhibited labeled somata in the present study. To explore the possibility that such neurons were labeled because their axons were transected and injury-filled as they coursed through the BPN injection site to enter the cerebellum via the brachium pontis, a series of rats received complete, bilateral lesions of the brachium pontis followed 30-60 minutes later with multiple, diffuse injections of WGA-HRP (12-16 placements per animal) throughout the cerebellar cortex. In another series of animals, the massive cerebellar WGA-HRP injections were not preceded by brachium pontis lesions. In the latter cases, each of the cell groups in question that were known to project directly to the cerebellum exhibited labeled somata. However, when the cerebellar HRP injections were preceded by brachium pontis lesions, each of the cell groups in question continued to exhibit labeled somata in numbers comparable to that observed in the nonlesion cases. This implies that such neurons project to the BPN and the cerebellar cortex and that the axons of these particular neurons do not project to the cerebellum via the brachium pontis.


Flexor tenosynovitis caused by Coccidioides immitis.
Coccidioidomycosis is a rare disease and dissemination of the pulmonary infection occurs in less than 0.1% of cases. A case report of coccidioidal tenosynovitis in association with immunosuppressive chemotherapy is described. Recommended management includes both intravenous amphotericin B and surgical synovectomy.


Optimizing granules size distribution for aerobic granular sludge stability: Effect of a novel funnel-shaped internals on hydraulic shear stress.
A novel funnel-shaped internals was proposed to enhance the stability and pollutant removal performance of an aerobic granular process by optimizing granule size distribution. Results showed up to 68.3±1.4% of granules in novel reactor (R1) were situated in optimal size range (700-1900μm) compared to less than 29.7±1.1% in conventional reactor (R2), and overgrowth of large granules was effectively suppressed without requiring additional energy. Consequently, higher total nitrogen (TN) removal (81.6±2.1%) achieved in R1 than in R2 (48.1±2.7%). Hydraulic analysis revealed the existence of selectively assigning hydraulic pressure in R1. The total shear rate (τtotal) on large granules was 3.07±0.14 times higher than that of R2, while τtotal of small granules in R1 was 70.7±4.6% in R2. Furthermore, large granules in R1 with intact extracellular polymeric substances (EPS) outer layer structure entrapped hydroxyapatite at center, which formed a core structure and further enhanced the stability of aerobic granules.


Curative haploidentical BMT in a murine model of X-linked chronic granulomatous disease.
Chronic granulomatous disease (CGD) is a primary immunodeficiency disorder characterized by defective microbial killing in phagocytes. Long-term prognosis for CGD patients is generally poor, highlighting the need to develop minimally toxic, curative therapeutic approaches. We here describe the establishment of a mouse model in which X-linked CGD can be cured by allogeneic bone marrow transplantation. Using a combination of non-myeloablative-dose total body irradiation and a single injection of anti-CD40 ligand monoclonal antibody, transplantation of whole bone marrow cells achieved long-lasting mixed chimerism in X-linked CGD mice in a haploidentical transplantation setting. Stable mixed chimerism was maintained for up to 1 year even at a low range (<20 % donor cells), indicating induction of donor-specific tolerance. The regimen induced mild myelosuppression without severe acute complications. Stable chimerism was therapeutic, as it suppressed cutaneous granuloma formation in an in vivo test suited for evaluation of treatment efficacy in murine CGD models. These results warrant future development of a simplified allogeneic hematopoietic cell transplantation regimen that would benefit CGD patients by allowing the use of haploidentical donor grafts without serious concerns of severe treatment-related toxicity.


Nonutility of cineurograms in children with congenital heart disease.
Cineurography is often performed after cineangiocardiography to look for occult congenital urinary tract disease. The accuracy of cineurography was investigated in 171 patients by comparing cineurograms with renal sonograms. One hundred fifteen cineurograms (67%) showed both kidneys well enough to allow assessment of renal structure and function and the results were confirmed in 112 by ultrasonography; 3 cineurograms yielded false-positive results. Limited or no information was obtained from cineurograms of 56 patients (33%) because of nonvisualization or poor visualization of 1 or both kidneys. Of the 11 patients (6%) with urinary tract disease, only 3 were correctly assessed by cineurography. Ultrasonography discovered all 11 renal abnormalities and produced only 1 false-positive result. These data indicate that cineurography is a poor screening test and should be abandoned. When uroradiologic screening is necessary for high-risk patients, sonography is recommended.


Synthesis of "dihydroacarbose", an alpha-D-glucosidase inhibitor having a pseudo-tetrasaccharide structure.
"Dihydroacarbose" (2), an alpha-D-glucosidase inhibitor having a pseudo-tetrasaccharide structure, was synthesized by reductive coupling of 4(3)-amino-1(1),6(1)-anhydro-2(1),3(1),2(2),3(2),6(2),2(3),3(3)-hepta-O- benzyl-4(3),6(3)-dideoxy-beta-maltotriose and 2D-(2,4/3,5)-2,3,4-tris(benzyloxy)-5-(trityloxymethyl)cyclohexa non e with sodium-cyanoborohydride. The former intermediate was prepared from a partially benzylated 1(1),6(1)-anhydro-beta-maltotriose, and the latter was prepared from a chiral, penta-substituted cyclohexene derived from D-glucose. The synthetic 2 was found to be a strong, non-competitive inhibitor (Ki = 1.13 x 10(-6) M) against small-intestinal sucrase of rat.


Morphometric analysis of subcortical structures in progressive supranuclear palsy: In vivo evidence of neostriatal and mesencephalic atrophy.
Progressive supranuclear palsy (PSP) is a neurodegenerative disease characterized by gait and postural disturbance, gaze palsy, apathy, decreased verbal fluency and dysexecutive symptoms, with some of these clinical features potentially having origins in degeneration of frontostriatal circuits and the mesencephalon. This hypothesis was investigated by manual segmentation of the caudate and putamen on MRI scans, using previously published protocols, in 15 subjects with PSP and 15 healthy age-matched controls. Midbrain atrophy was assessed by measurement of mid-sagittal area of the midbrain and pons. Shape analysis of the caudate and putamen was performed using spherical harmonics (SPHARM-PDM, University of North Carolina). The sagittal pons area/midbrain area ratio (P/M ratio) was significantly higher in the PSP group, consistent with previous findings. Significantly smaller striatal volumes were found in the PSP group - putamina were 10% smaller and caudate volumes were 17% smaller than in controls after controlling for age and intracranial volume. Shape analysis revealed significant shape deflation in PSP in the striatum, compared to controls; with regionally significant change relevant to frontostriatal and corticostriatal circuits in the caudate. Thus, in a clinically diagnosed and biomarker-confirmed cohort with early PSP, we demonstrate that neostriatal volume and shape are significantly reduced in vivo. The findings suggest a neostriatal and mesencephalic structural basis for the clinical features of PSP leading to frontostriatal and mesocortical-striatal circuit disruption.


Strain differences in behaviour and immunity in aged mice: Relevance to Autism.
The BTBR mouse model has been shown to be associated with deficits in social interaction and a pronounced engagement in repetitive behaviours. Autism spectrum disorder (ASD) is the most prevalent neurodevelopmental condition globally. Despite its ubiquity, most research into the disorder remains focused on childhood, with studies in adulthood and old age relatively rare. To this end, we explored the differences in behaviour and immune function in an aged BTBR T + Itpr3tf/J mouse model of the disease compared to a similarly aged C57bl/6 control. We show that while many of the alterations in behaviour that are observed in young animals are maintained (repetitive behaviours, antidepressant-sensitive behaviours, social deficits & cognition) there are more nuanced effects in terms of anxiety in older animals of the BTBR strain compared to C57bl/6 controls. Furthermore, BTBR animals also exhibit an activated T-cell system. As such, these results represent confirmation that ASD-associated behavioural deficits are maintained in ageing, and that that there may be need for differential interventional approaches to counter these impairments, potentially through targeting the immune system.


The role of X-linked genes in breast cancer.
While contribution of X chromosome in the susceptibility of prostate and ovarian cancer has been demonstrated, the role of X-linked genes in breast carcinogenesis is not clearly known. This study investigated and compared the X-linked gene expression profiles of MMTV-c-myc transgenic mammary tumor (MT) or MMTV-c-myc/MT-tgf-alpha double transgenic mouse mammary tumor (DT) to lactating mammary gland. cDNA microarray analysis using the Affymetrix system identified 1081 genes localized on the X chromosome with 174 and 194 genes at +/-2-fold change levels in MT and DT samples, respectively. Differentially expressed X-linked genes were predominantly related to chromatin structure/remodeling (e.g., Hdac8, Suv39h1, RbAp46 and Adr1), segregation (e.g., CENP-I and smc111) and, ribosomal biogenesis and translational control (e.g., Dkc1, Rpl44, Rpl39, Eif2s3x, Gspt2 and Rsk4). Confirmation of microarray data by semi-quantitative and quantitative RT-PCR in selected X-linked genes also showed similar pattern. In addition, the expression pattern of two chromosomal regions, XE3 and XF5, suggests that XE3 may have escaped from inactivation and XF5 subjected to inactivation. In conclusion, our data suggest that X-linked genes may play the key regulatory roles in the maintenance of chromatin structure, accurate chromosomal segregation and translational control; hence deregulation of X-linked genes may promote mammary gland tumorigenesis by promoting genetic instability and cell proliferation. Increased understanding of the role of X-linked genes and genetic pathways will provide the strategies to develop the molecular therapeutics to treat and prevent reproductive related cancers.


H(2) antagonist-induced thrombocytopenia: is this a real phenomenon?
Critically ill patients routinely receive H(2) antagonists for stress ulcer prophylaxis while at risk for gastrointestinal bleeding. In these patients it is often difficult to assess accurately the cause of adverse effects such as thrombocytopenia. We evaluate the literature to better define thrombocytopenia related to H(2) antagonist administration and discuss mechanism, potential as a risk factor and case reports describing the severity and duration of thrombocytopenia.


What limits for acute care in the elderly?
This review aims to address the important question of the increasing life expectancy and the aging population in the healthcare system today. We try to give some elements that will help the reflection about the ethical stakes balancing the necessity of care in the increasing number of elderly patients and the limited resources available, in the special context of acute care. There is growing evidence that the chronological age itself is not a reliable marker of bad prognosis or of mortality. The new concept of frailty may better correlate with the aging process of the elderly. The frailty index is an integrative approach considering the multiple factors impacting on the aging individual. Applied in the practical arena, it might become a useful tool for clinicians. Aging implies many biological modifications at molecular, cellular, organic levels as well as of the behavior. Some aspects of these processes and their consequences on health are described. The frailty concept is detailed, and its potential interest explained. We conclude that the measurement of aging phenomenon, including the frailty index, may help us to better assess the true health and the required therapeutics of elderly patients.


Differential effects of stress-induced cortisol responses on recollection and familiarity-based recognition memory.
Stress-induced changes in cortisol can impact memory in various ways. However, the precise relationship between cortisol and recognition memory is still poorly understood. For instance, there is reason to believe that stress could differentially affect recollection-based memory, which depends on the hippocampus, and familiarity-based recognition, which can be supported by neocortical areas alone. Accordingly, in the current study we examined the effects of stress-related changes in cortisol on the processes underlying recognition memory. Stress was induced with a cold-pressor test after incidental encoding of emotional and neutral pictures, and recollection and familiarity-based recognition memory were measured one day later. The relationship between stress-induced cortisol responses and recollection was non-monotonic, such that subjects with moderate stress-related increases in cortisol had the highest levels of recollection. In contrast, stress-related cortisol responses were linearly related to increases in familiarity. In addition, measures of cortisol taken at the onset of the experiment showed that individuals with higher levels of pre-learning cortisol had lower levels of both recollection and familiarity. The results are consistent with the proposition that hippocampal-dependent memory processes such as recollection function optimally under moderate levels of stress, whereas more cortically-based processes such as familiarity are enhanced even with higher levels of stress. These results indicate that whether post-encoding stress improves or disrupts recognition memory depends on the specific memory process examined as well as the magnitude of the stress-induced cortisol response.


pH-Activated surface charge-reversal double-crosslinked hyaluronic acid nanogels with feather keratin as multifunctional crosslinker for tumor-targeting DOX delivery.
Feather keratin (FK) was used as a multifunctional crosslinker for the fabrication of both pH responsive ionically and reduction responsive covalently crosslinked hyaluronic acid (HA) nanogels, as pH-activated surface charge-reversal double-crosslinked protein/polysaccharide complex nanocarriers for the tumor-targeting DOX delivery. The effect of the preparation condition on the diameter and the drug-loading capacity of the resultant drug delivery systems (DDSs) were investigated in detail. The in vitro controlled release profiles indicated the pH/reduction dual-responsive sustained release of DOX from the proposed double-crosslinked DOX@C-FK/HA nanogels. The in vitro experiments demonstrated that the DOX@C-FK/HA nanogels could be internalized into the HCT 116 cells via a CD44-receptor-mediated endocytosis pathway, exhibiting an enhanced anti-tumor efficacy than the free DOX.


Nature of methamphetamine-induced rapid and reversible changes in dopamine transporters.
The nature of methamphetamine-induced rapid and transient decreases in dopamine transporter activity was investigated. Regional specificity was demonstrated, since [3H]dopamine uptake was decreased in synaptosomes prepared from the striatum, but not nucleus accumbens, of methamphetamine-treated rats. Differences among effects on dopamine transporter activity and ligand binding were also observed, since a single methamphetamine administration decreased [3H]dopamine uptake without altering [3H]WIN35428 ([3H](-)-2-beta-carbomethoxy-3-beta-(4-fluorophenyl)tropane 1,5-naphthalenedisulfonate) binding in synaptosomes prepared 1 h after injection. Moreover, multiple methamphetamine injections caused a greater decrease in [3H]dopamine uptake than [3H]WIN35428 binding in synaptosomes prepared I h after dosing. Finally, decreases in [3H]dopamine uptake, but not [3H]WIN35428 binding, were partially reversed 24 h after multiple methamphetamine injections. Western blotting indicated that saline- and methamphetamine-affected dopamine transporters co-migrated on sodium dodecyl sulfate (SDS) gels at approximately 80 kDa, and that acute, methamphetamine-induced decreases in [3H]dopamine uptake were not due to loss of dopamine transporter protein. These findings demonstrate heretofore-uncharacterized features of the acute effect of methamphetamine on dopamine transporters.


Asymmetric stem cell division: lessons from Drosophila.
Asymmetric cell division is an important and conserved strategy in the generation of cellular diversity during animal development. Many of our insights into the underlying mechanisms of asymmetric cell division have been gained from Drosophila, including the establishment of polarity, orientation of mitotic spindles and segregation of cell fate determinants. Recent studies are also beginning to reveal the connection between the misregulation of asymmetric cell division and cancer. What we are learning from Drosophila as a model system has implication both for stem cell biology and also cancer research.


Toxic alcohol poisoning characteristics and treatments from 2000 to 2017 at a United States regional poison center.
Toxic alcohol exposures are an ongoing concern in the United States. In the US, few studies characterize the local epidemiology of toxic alcohols over time. The objective was to examine the incidence of toxic alcohol ingestions and changes in management over time. This retrospective cohort study evaluates toxic alcohol ingestion phone calls to a regional poison center in the United States covering four states. Data were queried for this poison center from the National Poison Data System (NPDS) using generic codes for each toxic alcohol. Inclusion criteria were ingestion of toxic alcohol, age ≥ 13 years, from January 1, 2000 to Dec 31, 2017. Exclusion criteria were unrelated effects coded in the medical outcome, duplicate data, or incomplete demographic data. Of 926 subjects (adults and teenagers), 71.5% were male, and the mean age was 34.5 years. Toxic alcohol ingestion was more common in individuals younger than 40 years, with a significant relationship between age and intentional abuse or misuse (p = 0.001). There was also a significant relationship between age and reason for ingestion, with younger patients more likely to be suicidal (p < 0.001). Ethyleneglycol was the most common toxic alcohol. There was no change in the incidence of toxic alcohol ingestions over the study period. The mortality rate was 1.7%, and 31.2%of patients were hospitalized in a critical care unit. Major effects and death were more common in younger patients (p < 0.001). There was a significant difference in medical outcomes based on the type of toxic alcohol(p = 0.03). Fomepizole was the most common treatment. A Poisson regression model found no change in fomepizole use during the study period (p = 0.1). Ethanol administration over the study period increased (p = 0.02), while hemodialysis decreased (p = 0.02). Data obtained from a single regional United States poison center showed low mortality related to toxic alcohol ingestions. The most prevalent toxic alcohol was Ethylene glycol. In all cases, toxic alcohol ingestion was higher in the 20-29-year-old age group. Reasons for ingestion, in most cases, were suicidal. Fomepizole was the most common treatment, ethanol administration as an antidote is rising, and hemodialysis utilization is decreasing. Data may not be nationally representative.


Reduced GS Domain Serine/Threonine Requirements of Fibrodysplasia Ossificans Progressiva Mutant Type I BMP Receptor ACVR1 in the Zebrafish.
Fibrodysplasia ossificans progressiva (FOP) is a rare human genetic condition characterized by altered skeletal development and extraskeletal bone formation. All cases of FOP are caused by mutations in the type I bone morphogenetic protein (BMP) receptor gene ACVR1 that result in overactivation of the BMP signaling pathway. Activation of the wild-type ACVR1 kinase requires assembly of a tetrameric type I and II BMP receptor complex followed by phosphorylation of the ACVR1 GS domain by type II BMP receptors. Previous studies showed that the FOP-mutant ACVR1-R206H required type II BMP receptors and presumptive glycine/serine-rich (GS) domain phosphorylation for overactive signaling. Structural modeling of the ACVR1-R206H mutant kinase domain supports the idea that FOP mutations alter the conformation of the GS domain, but it is unclear how this leads to overactive signaling. Here we show, using a developing zebrafish embryo BMP signaling assay, that the FOP-mutant receptors ACVR1-R206H and -G328R have reduced requirements for GS domain phosphorylatable sites to signal compared to wild-type ACVR1. Further, ligand-independent and ligand-dependent signaling through the FOP-mutant ACVR1 receptors have distinct GS domain phosphorylatable site requirements. ACVR1-G328R showed increased GS domain serine/threonine requirements for ligand-independent signaling compared to ACVR1-R206H, whereas it exhibited reduced serine/threonine requirements for ligand-dependent signaling. Remarkably, while ACVR1-R206H does not require the type I BMP receptor partner, Bmpr1, to signal, a ligand-dependent GS domain mutant of ACVR1-R206H could signal independently of Bmpr1 only when Bmp7 ligand was overexpressed. Of note, unlike human ACVR1-R206H, the zebrafish paralog Acvr1l-R203H does not show increased signaling activity. However, in domain-swapping studies, the human kinase domain, but not the human GS domain, was sufficient to confer overactive signaling to the Acvr1l-R203H receptor. Together these results reflect the importance of GS domain activation and kinase domain functions in regulating ACVR1 signaling and identify mechanisms of reduced regulatory constraints conferred by FOP mutations. © 2023 American Society for Bone and Mineral Research (ASBMR).


Multicomponent metal-organic framework nanocomposites for tumor-responsive synergistic therapy.
Targeted tumor therapy through tumor microenvironment (TME)-responsive nanoplatforms is an emerging treatment strategy used to enhance tumor-specificity to selectively kill cancer cells. Here, we introduce a nanosized zeolitic imidazolate framework-8 (ZIF-8) that simultaneously contains natural glucose oxidase (GOx) and Prussian blue nanoparticles (PBNPs) to construct multi-component metal-organic framework nanocomposites (denoted as ZIF@GOx@PBNPs), which possess cascade catalytic activity selectively within the TME. Once reaching a tumor site, GOx and PBNPs inside the nanocomposites are sequentially released and participate in the cascade catalytic reaction. In weak acidic TME, GOx, which effectively catalyzes the oxidation of intratumoral glucose to hydrogen peroxide (H2O2) and gluconic acid, not only initiates starvation therapy by cutting off the nutrition source for cancer cells but also produces the reactant for sequential Fenton reaction for chemodynamic therapy. Meanwhile, PBNPs, which are released from the ZIF-8 framework dissociated by acidified pH due to the produced gluconic acid, convert the generated H2O2 into harmful radicals to melanomas. In this way, the cascade catalytic reactions of ZIF@GOx@PBNPs enhance reactive oxygen species production and cause oxidative damage to DNA in cancer cells, resulting in remarkable inhibition of tumor growth. The tumor specificity is endowed by using the biomolecules overexpressed in TME as a "switch" to initiate the first catalytic reaction by GOx. Given the significant antitumor efficiency both in vitro and in vivo, ZIF@GOx@PBNPs could be applied as a promising therapeutic platform enabling starvation/chemodynamic synergism, high therapeutic efficiency, and minimal side effects.


Low level of microplastic contamination in wild fish from an urban estuary.
Microplastic accumulation in estuarine environments is considered the dominant input of land-based plastics into the oceans. In this study, the level of microplastic contamination was evaluated in 26 species of wild fish from the Pearl River Estuary, South China. Results showed that microplastics abundance ranged from 0.17 items individual-1 (Boleophthalmus pectinirostris & Acanthogobius flavimanus) to 1.33 items individual-1 (Plectorhynchus cinctus) among different species. The distribution of microplastic abundance in the gills and gastrointestinal tracts was not significantly different. Microplastics in gills are strongly related to the filtration area of gills in 15 fish species. Fibers were the dominant shapes accounting for 93.45% of the total shapes. The majority of microplastics were <3 mm in size. The most common polymer composition was polyethylene terephthalate (38.2%) and the most common color was black (30.36%). The findings of this study provide baseline data for microplastic contamination in wild fish from an urban estuary.


Individual-level and plant-level predictors of acute, traumatic occupational injuries in a manufacturing cohort.
Workplace and contextual factors that may affect risk for worker injury are not well described. This study used results from an employee job satisfaction survey to construct aggregate indicators of the work environment and estimate the relative contribution of those factors to injury rates in a manufacturing cohort. Principal components analysis was used to construct four plant-level factors from responses to a 32 question survey of the entire workforce, administered in 2006. Multilevel Poisson regression was used to evaluate the relationship between injury rate, individual-level and plant-level risk factors, unionisation and plant type. Plant-level 'work stress' (incident rate ratio (IRR)=0.50, 95% CI 0.28 to 0.90) was significant in the multilevel model, indicating the rate of injury for an average individual in that plant was halved (conditional on plant) when job stress decreased by a tertile. 'Overall satisfaction', 'work environment' and 'perception of supervisor' showed the same trend but were not significant. Unionisation was protective (IRR=0.40, 95% CI 0.17 to 0.95) as was any plant type compared with smelter. We demonstrated utility of data from a human resources survey to construct indicators of the work environment. Our research suggests that aspects of the work environment, particularly work stress and unionisation, may have a significant effect on risk for occupational injury, emphasising the need for further multilevel studies. Our work would suggest monitoring of employee perceptions of job stress and the possible inclusion of stress management as a component of risk reduction programmes.


Having children after surviving cancer in childhood or adolescence - results of a Berlin survey.
To assess the desire to have children, the actual number of children, and children's health in a survey of 752 adult survivors of paediatric or adolescent cancer in Berlin, Germany. The German Childhood Cancer Registry ( Deutsches Kinderkrebsregister, DKKR) listed 752 paediatric cancer patients who had been treated in 1 of the 2 paediatric oncology centres in Berlin since 1980 and were 18 years of age or older at the time of the survey. A 4-page questionnaire assessing pubertal development, fertility, the desire to have children, the actual number of children, and children's health was sent to 574 former patients located using data from the DKKR and German Residents' Registration Office. In total, 45% (n=260) of patients (140 women, 120 men) returned the questionnaire. The mean age was 10.9 years at the time of diagnosis and 24.3 years at the time of the present survey. Various aspects of puberty were assessed to evaluate pubertal development. Of all study participants, 77% indicated a general desire to have children. Reasons given for not having children included 'Still too early to have children' (67%), 'Fear that my child will develop cancer' (9%), and 'Fear that cancer will recur' (6%). Transient amenorrhoea, lasting from 1 to 30 months, occurred in 25 of 74 patients after chemo- and radiotherapy. Five of 136 participants indicated that they had already reached menopause. Seventeen per cent of all participants or their partners had already been pregnant. The miscarriage rate was 13%. Thirty participants gave birth to or fathered a total of 41 children, of whom 40 were healthy and 1 was born with a foot deformity (Pes equinovarus). Among participants' children, mean weight at birth was 3 458 g, and mean head circumference was 35 cm. The desire to have children was lower among our survey participants than in the general population of the same age (77% vs. 90%). Participants' fears that their children might develop cancer or that their own cancer might recur are often unfounded. Paediatric cancer survivors, relatives, and attending physicians should be well informed about this issue by paediatric oncologists. The proportion of miscarriages, mean weight at birth, and mean head circumference at birth in our study were comparable to the German general population. We intend to conduct a nationwide survey entitled 'Fertility after Chemo- and Radiotherapy in Paediatric and Adolescent Patients' (FeCt). The aim is to gain valuable data with a larger number of participants and more statistical power to determine whether specific cytotoxic drugs or radiation increase the risk of infertility, and if so, at what doses. For the study, the DKKR has the addresses of more than 5 000 former patients in Germany who are now adults. The results will be used to plan future treatment optimisation studies, and to assess the need for prophylactic measures in cases where fertility-compromising therapies are unavoidable. This nationwide survey 'FeCt' will be supported by the Deutsche Kinderkrebsstiftung.


The development of a novel oral 5-Fluorouracil in-situ gelling nanosuspension to potentiate the anticancer activity against colorectal cancer cells.
5-Fluorouracil is an anticancer drug with a short biological half-life. This study aimed to develop oral sustained-release nano-formulations of 5-Fluorouracil. 5-Fluorouracil-carrageenan coated particles were prepared and characterized. To formulate a suspension, the coated particles were encapsulated in an aqueous hydrodynamic gel of sodium alginate with carrageenan-lambda or chitosan in excess, and the optimum suspension was determined using drug release analysis, gel characterization, and particle size analysis. Afterward, the optimal formulation was tested against colorectal cancer cells to assess the cell viability, level of apoptosis, and caspase-9 activity. Interestingly, the sustained-release formulations with the best ability to form a coherent insoluble sedimented gel when in contact with 0.1 N hydrogen chloride were the F5 and F6 formulations. Moreover, those formulations were nanosuspensions (20-63 nm) and the 5-Fluorouracil nanoparticles released from them were coated with carrageenan and sodium alginate. After the antitumor characterization against HCT-116 cells, the 5-Fluorouracil nanoparticle formulation was approved for its contribution to the sustained-release characteristics, sensitivity, and time-dependent efficacy. This nanosuspension is suggested to serve as a long-acting therapy, which it could protect the drug nanoparticles through the pH-selective and sustained release matrix, in-situ gel formation in the stomach, and the polymer coating of the released nano-drug particles.


The role of a trial of labor with a positive contraction stress test.
During a 28 month period 812 patients underwent antepartum FHR testing. Twenty-eight patients had a positive CST. There were two antepartum fetal deaths and 11 patients had a cesarean section without a trial of labor. Fifteen patients had a trial of closely monitored labor (continuous FHR and fetal scalp blood sampling when indicated) and 11 of these (73%) were delivered vaginally. The CST records were examined for: per cent late deceleration, baseline FHR, presence of FHR accelerations, duration of the latency period (time from onset of contraction to onset of deceleration), and amplitude of deceleration. The absence of accelerations (nonreactive CST) and a latency period of less than 45 seconds both predicted persistent late deceleration during labor or fetal death in utero but statistical significance was found only for the latter parameter.


Effects of light and temperature on leaf anatomy and photosynthesis in Fragaria vesca.
Fragaria vesca, the woodland strawberry, was grown under a series of controlled environments including variations in light intensity, average temperatures, and temperature amplitude around a constant mean. Observations on CO2 exchange capacities, leaf anatomy, and cell ultrastructure were made for each treatment to determine relationships between these variables. With increasing light intensity, leaf thickness, leaf density, and mesophyll cell surface area and volume per leaf surface area increased. Net photosynthesis (NPS) per leaf weight decreased with increasing light pretreatment while NPS per area increased from low to medium intensity, then decreased at the highest intensity. Depression of photosynthesis at the highest light pretreatment may have been due to massive starch accumulation in the chloroplasts associated with the sodium vapor lamps used. Correlation of all anatomical variables was highly significant with dark respiration and NPS per dry weight but insignificant for NPS per leaf area. In the variable temperature treatments, photosynthetic acclimation occurred with a shift in optimum temperature for NPS in the direction of prevailing growth temperature. Absolute rates were highest at moderate pretreatment temperatures and were reduced by extreme growth temperatures. Thick leaves with low density mesophyll became thinner and more dense with increasing growth temperature corresponding to an increase in maximum net photosynthetic rates. Leaves became thicker and more dense at the highest temperatures, but with an increase in cell damage and indications of changes in metabolic pathways. Highest correlations for gas exchange rates were with specific leaf weight (weight per area). Correlation with other anatomical variables were scattered or insignificant. It was concluded that adaptation to a range of environmental conditions cannot be consistently attributed to changes in mesophyll cell volume or surface area.


Effect of nifedipine on the motility of the sphincter of Oddi and small bowel of the opossum.
The effect of the calcium-channel blocker nifedipine on the electromyographic activity of the small bowel and sphincter of Oddi was studied in conscious opossums. Electromyographic and arterial pressure recordings were started 7-10 days after implantation of seven pairs of electrodes along the small bowel and sphincter of Oddi. Continuous infusion of nifedipine caused a dose-dependent reduction of the frequency of spike bursts in the small bowel and sphincter of Oddi. Nifedipine at high doses abolished the migrating motor complex in the gastrointestinal tract. The frequency of slow waves was unchanged. This drug possibly inhibits the membrane influx of calcium into the smooth muscle cells of the gastrointestinal tract. We conclude that nifedipine causes an intense decrease in the motility of the small bowel and sphincter of Oddi.


Effects of live-trapping and toe-clipping on body weight of European and African rodent species.
Changes in body weights of four species of small rodents were monitored to evaluate the method of toe-clipping for individual identification. If carefully applied the method was found to be without any biologically meaningful effects on the animals. Secondly, body weight changes in prolonged live-trapping studies were evaluated in five species of small rodents. It was found that the animals generally do not recover from the stress of trapping within 24 h. Absolute weight losses were small on a daily basis but mounted up when animals were trapped day after day.


Resistance to Immunotherapy: Mechanisms and Means for Overcoming.
Immune checkpoint blockade transformed cancer therapy during the last decade. However, durable responses remain uncommon, early and late relapses occur over the course of treatment, and many patients with PD-L1-expressing tumors do not respond to PD-(L)1 blockade. In addition, while some malignancies exhibit inherent resistance to treatment, others develop adaptations that allow them to evade antitumor immunity after a period of response. It is crucial to understand the pathophysiology of the tumor-immune system interplay and the mechanisms of immune escape in order to circumvent primary and acquired resistance. Here we provide an outline of the most well-defined mechanisms of resistance and shed light on ongoing efforts to reinvigorate immunoreactivity.


Effect of phototherapy on growth of low-birth-weight infants--two-year follow-up.
The effect of phototherapy on subsequent growth of low-birth-weight infants has been evaluated at two-year follow-up of infants from two separate controlled neonatal studies. Growth of weight, length, and head circumference in the treated infants of Group I was slower than that of control subjects. Growth was comparable in treated infants and control subjects in Group II, and the two control groups, although not concurrent were also similar. Infants whose heads were growing at a normal rate, even though below 2 SD from the norms, were developing normally. Only infants who had deceleration in rate of head growth were abnormal. It is unlikely that phototherapy was responsible for the slow growth patterns seen in Group I, since these patterns were not reproducible in Group II.


pH-profile crystal structure studies of C-terminal despentapeptide nitrite reductase from Achromobacter cycloclastes.
Crystal structures of C-terminal despentapeptide nitrite reductase (NiRc-5) from Achromobacter cycloclastes were determined from 1.9 to 2.3A at pH 5.0, 5.4, and 6.2. NiRc-5, that has lost about 30% activity, is found to possess quite similar trimeric structures as the native enzyme. Electron density and copper content measurements indicate that the activity loss is not caused by the release of type 2 copper (T2Cu). pH-profile structural comparisons with native enzyme reveal that the T2Cu active center in NiRc-5 is perturbed, accounting for the partial loss of enzyme activity. This perturbation likely results from the less constrained conformations of two catalytic residues, Asp98 and His255. Hydrogen bonding analysis shows that the deletion of five residues causes a loss of more than half the intersubunit hydrogen bonds mediated by C-terminal tail. This study shows that the C-terminal tail plays an important role in controlling the conformations around the T2Cu site at the subunit interface, and helps keep the optimum microenvironment of active center for the full enzyme activity of AcNiR.


Association of Neuroprotective Effect of Di-O-Demethylcurcumin on Aβ25-35-Induced Neurotoxicity with Suppression of NF-κB and Activation of Nrf2.
Amyloid-β peptides (Aβ), a major component of senile plaques, play an important role in the development and progression of Alzheimer's disease. Several lines of evidence have demonstrated that Aβ-induced neuronal death is mediated by oxidative stress. The present study aimed to evaluate the potential involvement of di-O-demethylcurcumin, an analog of curcuminoid, on Aβ-induced neurotoxicity in culture neuroblastoma cells (SK-N-SH cells) through the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway and the suppression of nuclear factor-κB (NF-κB) signaling pathway and their downstream targets. The results showed that pretreatment with di-O-demethylcurcumin elevated cell viability and decreased the level of reactive oxygen species. Moreover, treatment with di-O-demethylcurcumin promoted the translocation of Nrf2 protein from the cytoplasm to the nucleus, increased the expression of Nrf2-ARE pathway-related downstream proteins including heme oxygenase (HO-1), NAD(P)H:quinone oxidoreductase 1 and glutamate-cysteine ligase catalytic subunit, and increased the activity of superoxide dismutase enzymes. On the other hand, di-O-demethylcurcumin suppressed the degradation of IκBα, translocation of the p65 subunit of NF-κB from cytoplasm to nucleus and thereby, attenuated the expression of inducible nitric oxide synthase protein and nitric oxide production. Taken together, these results suggest that neuroinflammatory effect of di-O-demethylcurcumin might potentially be due to inhibit NF-κB and activate Nrf2 signaling pathways induced by Aβ25-35.


Knee rotational laxity and proprioceptive function 2 years after partial ACL reconstruction.
The aim of our study was to evaluate knee rotational laxity and proprioceptive function 2 years after partial anterior cruciate ligament (ACL) reconstruction. According to our hypothesis, partial ACL reconstruction could restore knee laxity and function to the intact level. We conducted a study in fifteen consecutive patients undergoing partial ACL reconstruction. Fifteen anteromedial bundle tears were identified intraoperatively. Partial ACL reconstructions were performed by the same senior surgeon using a single-incision technique. A bone-patellar tendon-bone graft was used in 13 cases and a double-stranded semitendinosus graft in 2 cases of chronic patellar tendonitis. The mean age at surgery was 29 years. The time between ACL tear and surgery averaged 7.8 months (range 2.5-29.5 months). We developed an original device designed to assess knee proprioception (passive and active) and measure weight-bearing rotational laxity in full extension and at 30°, 60° and 90° of knee flexion. All measurements were taken on both the reconstructed and healthy knee. The mean follow-up of the study was 3.4 years (range 2.6-4.4). No statistically significant difference in rotational laxity, active or passive proprioception could be observed between the reconstructed and healthy knee. External rotation was significantly greater than internal rotation in full extension and at 30° of flexion in the reconstructed and the healthy knee (P < 0.05). For each knee, active proprioception was found to be significantly different (higher) than passive proprioception (P < 0.05). Our study did not detect any difference in rotational laxity and proprioception between the reconstructed and the healthy knee. Therefore, partial ACL reconstruction appears to restore satisfactory knee laxity and function in case of partial ACL tear. IV.


Vasorelaxant property of 2-phenyl ethyl alcohol isolated from the spent floral distillate of damask rose (Rosa damascena Mill.) and its possible mechanism.
Rosa damascena Mill. (Rosaceae), commonly known as damask rose, is an ancient medicinal and perfumery plant used in Traditional Unani Medicine due to various therapeutic effects, including cardiovascular benefits. This study aimed to evaluate the vasorelaxant effect of the 2-phenyl ethyl alcohol (PEA) isolated from the spent flowers of R. damascena which remain after the extraction of essential oil. The freshly collected flowers of R. damascena were hydro-distilled in a Clevenger's type apparatus to extract the rose essential oil (REO). After removing the REO, the spent-flower hydro-distillate was collected and extracted with organic solvents to yield a spent-flower hydro-distillate extract (SFHE), which was further purified by column chromatography. The SFHE and its isolate were characterized by gas chromatography (GC-FID), gas chromatography-mass spectrometry (GC-MS), and nuclear magnetic resonance (NMR) techniques. The PEA, isolated from SFHE, was evaluated for vasorelaxation response in conduit blood vessels like rat aorta and resistant vessels like mesenteric artery. The preliminary screening of PEA was done in aortic preparation pre-constricted with phenylephrine/U46619. Further, a concentration-dependent relaxation response to PEA has been elicited in both endothelium-intact and endothelium-denuded arterial rings, and the mode of action was explored. The SFHE revealed the presence of PEA as the main constituent (89.36%), which was further purified by column chromatography to a purity of 95.0%. The PEA exhibited potent vasorelaxation response both in conduit vessels like the rat aorta and resistance vessels like the mesenteric artery. The relaxation response is mediated without any involvement of vascular endothelium. Further, TEA sensitive BKCa channel was found to be the major target for PEA-induced relaxation response in these blood vessels. The spent flowers of R. damascena, which remain after the extraction of REO, could be used to extract PEA. The PEA possessed marked vasorelaxation properties in both aorta and mesenteric artery and showed promise for development into an herbal product against hypertension.


Neutralizing activity and protective immunity to ricin toxin conferred by B subunit (RTB)-specific Fab fragments.
SylH3 and 24B11 are murine monoclonal antibodies directed against different epitopes on ricin toxin's binding (RTB) subunit that have been shown to passively protect mice against ricin challenge. Here we report that Fab fragments of SylH3 and 24B11 neutralize ricin in a cell based assay, and in a mouse challenge model as effectively as their respective full length parental IgGs. These data demonstrate that immunity to ricin can occur independent of Fc-mediated clearance.


Emergence of coexistence of a novel blaNDM-5-harbouring IncI1-I plasmid and an mcr-1.1-harbouring IncHI2 plasmid in a clinical Escherichia coli isolate in China.
Co-harbouring of carbapenem and colistin resistance genes in multidrug-resistant Enterobacterales strains poses a serious public health problem. In this study, an MCR-1.1 and NDM-5 coproducing Escherichia coli strain named EC6563 was isolated and characterized. This study aimed to characterize a clinical carbapenem-resistant E. coli isolate which co-harbours mcr-1.1 and blaNDM-5 on separate plasmids, and explored the phenotypic and genotypic characteristics of the mcr-1.1- and blaNDM-5-harbouring plasmids. E. coli isolate EC6563 was subjected to antimicrobial susceptibility testing, conjugation assay, stability of the plasmid and growth rate determination. In addition, the whole genome sequence of this strain was obtained and the genetic characteristics of the mcr-1.1- and blaNDM-5-harbouring plasmids were analyzed. Carbapenem-resistant E. coli isolate EC6563 was resistant to all the tested antibiotics except tigecycline. Bioinformatic analysis confirmed that the IncHI2 plasmid carrying mcr-1.1 was highly similar to the previously reported mcr-1.1-harbouring plasmid pGDP37-4, and carried multiple drug resistance genes and the IncI1-I plasmid carrying blaNDM-5 had low similarity to the published blaNDM-5-carrying IncI1-I plasmid pEC-16-10-NDM-5. The pEC6563-NDM5 plasmid was capable of conjugation with an efficiency of 1.34 × 10-2 in a filter mating experiment. The transconjugant J53/pEC6563-NDM5 was able to be stably inherited after 12 days of passage. To the best of our knowledge, this is the first time that an IncHI2 plasmid carrying mcr-1.1 and an IncI1-I plasmid carrying blaNDM-5 is found to coexist in an E. coli isolate. Our research expands the known diversity of plasmids in NDM-5-producing Enterobacterales strains. Meanwhile, effective measures should be taken to prevent the spread of these plasmids.


Oncological Outcomes of Major Liver Resection Following Portal Vein Embolization: A Systematic Review and Meta-analysis.
Preoperative portal vein occlusion with either percutaneous portal vein embolization (PVE) or portal vein ligation is routinely used to induce liver hypertrophy prior to major liver resection in patients with hepatic malignancy. While this increases the future liver remnant, and hence the number of patients suitable for resection, recent evidence suggests that induction of liver hypertrophy preoperatively may promote tumor growth and increase recurrence rates. The aims of this current study were to evaluate the impact of PVE on hepatic recurrence rate and survival in patients with colorectal liver metastases (CRLM). The MEDLINE, EMBASE and Web of Science databases were searched to identify studies assessing the oncological outcomes of patients undergoing major liver resection for CRLM following PVE. Studies comparing patients undergoing one-stage liver resection with or without preoperative PVE were included. The primary outcome was postoperative hepatic recurrence (PHR), while secondary outcomes were 3- and 5-year overall survival (OS). Of the 2131 studies identified, six non-randomized studies (n = 668) met the eligibility criteria, comparing outcomes of patients undergoing major liver resection with or without PVE (n = 182 and n = 486, respectively). No significant difference was observed in PHR (odds ratio [OR] 0.78; 95 % confidence interval [CI] 0.42-1.44), 3-year OS (OR 0.80; 95 % CI 0.56-1.14) or 5-year OS (OR 1.12; 95 % CI 0.40-3.11). PVE does not have any adverse effect on PHR or OS in patients undergoing major liver resection for CRLM. Further studies based on individual patient data are needed to provide definitive answers.


Workplace bullying among nurses and organizational response: An online cross-sectional study.
To examine prevalence of bullying among nurses and explore associations of organizational betrayal and support with well-being among nurses exposed to bullying. Bullying is a problem in many nursing workplaces, and organizations have an obligation to support nurses who are bullied. Support or betrayal after bullying could affect nurse well-being, including burnout. In this cross-sectional study among U.S. nurses, data were collected in a survey using the Negative Acts Questionnaire-Revised for Nursing, the Institutional Betrayal Questionnaire for Health, the Well-Being Index, a job satisfaction scale and demographic questions. Prevalence of weekly/daily bullying was 31% (N = 242). Among nurses exposed to any bullying (N = 173), organizational betrayal increased odds of burnout (OR 2.62, p = .02), job dissatisfaction (OR 2.97, p = .04) and absenteeism (OR 6.11, p < .001). Organizational support decreased odds of job dissatisfaction (OR 0.30, p = .001) and absenteeism (OR 0.50, p = .04). Analysis of study findings suggests organizational betrayal increases likelihood of burnout, job dissatisfaction and absenteeism, and support decreases likelihood of dissatisfaction and absenteeism. Nurse leaders should be aware of the issue of organizational betrayal and support in relation to well-being. Future studies can further explore the concepts of betrayal and support to provide additional evidence.


FcγRIIB expression increases during primary biliary cholangitis.
Primary biliary cholangitis (PBC) is a severe disease with unknown aetiology and poor prognosis owing to ineffective treatment. B-cell antibodies play a regulatory role during immune responses; therefore, their role in PBC should not be overlooked. Fcγ receptors (FcγRs) of IgG and cell surface glycoproteins play an important role in autoimmune and infectious disease prevention. In this study, 60 patients with PBC and 35 healthy controls (HCs) were recruited. The number of B cells and the expression of the FcγRIIB on the peripheral blood mononuclear cells of patients with PBC were evaluated using FACS. The concentrations of soluble FcγRs were determined using ELISA, and intrahepatic FcγRIIB and CD19 expressions in patients with PBC were visualised using IHC. FcγRIIB expression in B cells was significantly higher in patients with PBC than in HCs (P < 0.0001). The soluble FcγRIIB levels in the plasma were higher in patients with PBC than in HCs (P = 0.0009). Notably, these levels were reduced by treatment with ursodeoxycholic acid (P = 0.0236). CD19 and FcγRIIB expression increased in the liver of patients with PBC relative to that in HCs. These findings can provide new insights into PBC pathogenesis and can aid the future development of treatment strategies.


Magnetic resonance quantification of skeletal muscle lipid infiltration in a humanized mouse model of Duchenne muscular dystrophy.
Rodent models of Duchenne muscular dystrophy (DMD) often do not recapitulate the severity of muscle wasting and resultant fibro-fatty infiltration observed in DMD patients. Having recently documented severe muscle wasting and fatty deposition in two preclinical models of muscular dystrophy (Dysferlin-null and mdx mice) through apolipoprotein E (ApoE) gene deletion without and with cholesterol-, triglyceride-rich Western diet supplementation, we sought to determine whether magnetic resonance imaging and spectroscopy (MRI and MRS, respectively) could be used to detect, characterize, and compare lipid deposition in mdx-ApoE knockout with mdx mice in a diet-dependent manner. MRI revealed that both mdx and mdx-ApoE mice exhibited elevated proton relaxation time constants (T2 ) in their lower hindlimbs irrespective of diet, indicating both chronic muscle damage and fatty tissue deposition. The mdx-ApoE mice on a Western diet (mdx-ApoEW ) presented with greatest fatty tissue infiltration in the posterior compartment of the hindlimb compared with other groups, as detected by MRI/MRS. High-resolution magic angle spinning confirmed elevated lipid deposition in the posterior compartments of mdx-ApoEW mice in vivo and ex vivo, respectively. In conclusion, the mdx-ApoEW model recapitulates some of the extreme fatty tissue deposition observed clinically in DMD muscle but typically absent in mdx mice. This preclinical model will help facilitate the development of new imaging modalities directly relevant to the image contrast generated in DMD, and help to refine MR-based biomarkers and their relationship to tissue structure and disease progression.


Simultaneous mitigation of Cd and As availability in soil-rice continuum via the addition of an Fe-based desulfurization material.
The simultaneous mitigation of toxic arsenic (As) and cadmium (Cd) in rice grain remains a global challenge. Passivation with natural or artificially modified materials has shown great potential to simultaneously reduce the bioavailability of As and Cd in paddy soils. To date, however, limited materials have are available, with unclear underling mechanisms. Here, a natural iron-based desulfurization material is hypothesized to simultaneously mitigate As and Cd availability in paddy soil-rice continuum, since it is rich in calcium (Ca), iron (Fe), Silicon (Si), manganese (Mn), and sulfur (S). The addition of the proposed material promoted rice growth and reduced soil availability of Cd (extracted with 0.01 mg·L-1 of CaCl2) by 88.0-89.6% and As (extracted with 0.5 mg·L-1 of KH2PO4) by 37.9-69.9%. Grain Cd was reduced by 26.4-51.6%, whereas that of inorganic As (iAs) by 33.3-42.7%. The increased Fe (by 44.2%) and Mn (by 178.6%) in iron plaque on the root surface were conducive to the reduction of grain Cd and iAs after application. Furthermore, the maximum adsorption capacities of the proposed material for Cd and As(III) reached 526.31 and 2.67 mg·g-1, respectively. The coprecipitation with Cd(OH)2 as a product, Fe-As and Ca-As complexation, and ion exchange of Fe2+ released by the material with Cd2+ are involved in the mechanisms underlying the available As and Cd reduction. Combining the safety, low-cost, and high accessibility, Fe-based desulfurization material showed great potential for future safe-utilization of As-Cd contaminated paddy soil via passivation.


Delineation of partial melts and crustal heterogeneities within the crust beneath Kumaon Himalaya, India from Lg wave attenuation.
The crustal seismic attenuation or the Q structure is studied by using the Fourier spectra of Lg-wave along the Tanakpur- Dharchula- Dharma transect in the Kumaon Himalaya. The 1 Hz Lg Q (Q0) values are computed between different pairs of two stations and the observed values are later utilized to calculate the lateral variation in the Q0 values by following a back projection algorithm. This computation of Q0 values utilizes five regional distance earthquakes having moment magnitude (Mw) ≥ 4.0, which lie along the great circle path of the transect. Three of the five earthquakes occurred in the Tibetan plateau and the and the others occurred to the southwest on the Indian shield and are well recorded at all the 32 broadband seismographs operated between September 2018 and March 2022. The estimate Qo values range from 63 ± 2 and 203 ± 25, with the lowest value in the Lesser Himalaya and the highest across part of the Indo Gangetic Plain and Siwalik Himalaya. The Q0 model has low values ∼200 along the profile in the Indo Gangetic Plain and the Siwalik Himalaya, and are correlated with 2-5 km thick sedimentary layers below the Himalaya and the adjoining Indo-Gangetic Plain. We observe two distinctly different Q0 values to the northeast in the Lesser Himalaya tectonic unit. The region lying between the South Almora Thrust (SAT) and the Berinag Thrust (BT) shows extremely low Q0 values (∼60) but increases further north towards the Vaikrita Thrust (VT) to ∼200. The possible explanation for observing such huge variation of the Q0 values within a single tectonic unit may be the presence of fluid rich ramp structures, which introduces crustal heterogeneities and traps the aqueous fluids or partial melts lying within the crust. The Lg Q0 values decrease to the North and become ∼166 for station pairs in the Higher Himalaya and Tethys Himalaya tectonic units. The low Q0 values observed in this region may be correlated with low viscous partial melts in the form of Miocene leucogranite plutons, which resulted out of the Indo-Asian collision. The attenuation structure along the profile in the Kumaon Himalaya can be used to estimate ground motions of future earthquakes in the area and can contribute to seismic hazard assessment in the Himalaya and neighbouring regions.


Protein synthesis after experimental injury in pigs. A comparison of infusion solutions with different amino acid patterns.
This study compared the effect of three amino acid solutions on protein metabolism after injury by measuring plasma amino acid pattern, nitrogen balance, total body protein synthesis and utilisation of administered nitrogen in an experimental protocol using pigs. Protein synthesis and nitrogen utilisation were determined using a 15N-tracer technique with recourse to mathematical model concepts. Control animals which had not undergone surgery had a lower urinary nitrogen excretion, a more favourable nitrogen balance, greater total body protein synthesis and utilisation of the infused amino acids during the infusion of an amino acid solution with a standard pattern of amino acids (A) than the operated animals infused with either solution A or two other test amino acid solutions B and C. Comparison of the post-operative data showed that if solution A is compared with solution (B) whose amino acid content takes account of changes in plasma amino acids following trauma and a solution (C) which contains a high fraction of branched chain amino acids, solution (B) yields the best results in respect of total body protein synthesis and nitrogen utilisation.


Davis flap: the glory still present.
Upper third defects of the ear are too large to be closed primarily without distorting the auricle. Full thickness defects can be reconstructed with local flaps. In this article, Davis flap was used to fill the upper third defects of the ear with some modifications. Eight patients underwent reconstruction of full thickness auricular defects with Davis flaps from July 2012 to December 2014. The posterior surface of the flap and the raw area of conchal area were covered by full thickness graft taken from posterior surface of ear. All flaps survived. No congestion was noted. The donor sites and skin grafts healed uneventfully. Davis flap is a simple and reproducible tool for reconstruction of upper third of ear.


Impact of gefitinib ('Iressa') treatment on the quality of life of patients with advanced non-small-cell lung cancer.
Patients with advanced non-small-cell lung cancer (NSCLC) have a short life expectancy; therefore, in addition to increasing their survival, improving their quality of life (QoL) is also an important treatment goal. We evaluated the QoL of patients with advanced NSCLC who were unfit to receive chemotherapy, failed to respond or progress following prior chemotherapy, who received subsequent treatment with gefitinib ('Iressa') on a compassionate use basis, using a standard QoL questionnaire, (EORTC) QLQ-C30 and the related lung cancer-specific module QLQ-LC13. Analysis of the functional scales showed a trend towards improvement for role, emotional and cognitive scales, while a substantial stability was seen for general QoL scale. Analysis of the symptoms scales of QLQ-C30, showed a trend towards improvement for fatigue, dyspnoea, insomnia, and constipation, after one month of therapy. Fifty-six of the 57 patients were considered evaluable for response. One patient evidenced a partial response (patient is still on response), 29 patients had stable disease for a median duration of 5 months (range 4-7 months), and 26 patients progressed. After treatment with Gefitinib, we observed maintenance of QoL in a group of patients with poor prognosis that would be expected to have a worsening QoL. Furthermore important symptoms like dyspnoea fatigue and pain in other parts, that usually afflict patients with NSCLC, showed a trend toward improvement after only one month of therapy.


Respiratory activities of hepatocytes isolated from rats of various ages. A brief note.
The ratio between the oxygen consumption of isolated hepatocytes in the presence of an inhibitor of oxidative phosphorylation (oligomycin, atractyloside) and in the presence of an uncoupler (dinitrophenol) is used as an estimation of the respiratory control ratio of mitochondria inside the isolated liver parenchymal cell. No significant age-related decline in the functional integrity of the mitochondria could be detected.


What motivates individuals to volunteer in Ebola epidemic response? A structural approach in Guinea.
The 2014-2016 Ebola epidemic in West Africa placed greater demands on the affected countries' already scarce health workforce. Consequently, governments in the most affected West African countries made appeals for volunteers to join Ebola response programs. Those volunteers played an important yet high-risk role in aiding the victims of the Ebola epidemic and in limiting its spread. However, little is known as to what motivated those volunteers to commit themselves to the Ebola response programs. This information is important for planning for volunteer recruitment strategies during future epidemics. The aim of the present study, therefore, was to identify and assess the motivations that led individuals to volunteer for Ebola response programs in West Africa. The study participants were 600 persons who volunteered through the Guinean Ebola response program during the 2014-2016 epidemic. From February to May 2016, they were presented with a questionnaire that contained 50 assertions referring to possible motives for volunteering in the Ebola response program and indicated their degree of agreement with each of them on a scale of 0-10. The responses were analyzed using factor analysis. Seven separable volunteer motivations were identified. "Feeling of patriotic duty" (M = 9.02) and "Feeling of moral responsibility" (M = 8.12) clearly emerged as the most important. Second-tier motivations were "Compliance with authority" (M = 6.66), "Desire to use one's skills for a collective good" (M = 6.49), "Seeking personal growth" (M = 5.93), "Desire to gain community recognition" (M = 5.13), and "Hoping for a career reorientation" (M = 4.52). These findings strongly suggest that volunteer recruitment, if needed in future Ebola epidemics, must adopt a multifaceted motivational approach rather than focus on one single motivator. Putting relatively more emphasis on motivational messages referring to patriotic values, as well as to moral responsibility, would likely increase volunteering.


Mapping alveolar binding sites in vivo using phage peptide libraries.
Targeting lung tissue is nonselective due in part to the lack of specific cell-surface receptors identified on target lung cells. We used in vivo phage display to identify a panel of peptides that can bind selectively to lung epithelial cells with less binding to nonepithelial cells. By direct intratracheal instillation of phage libraries into the lung, we isolated and identified 143 individual phage clones. Three phage clones revealed enhanced binding to the lung in vitro and in vivo. These three identified peptides were synthesized and demonstrated selective binding to epithelial cells in lung tissue versus the control peptide. Further, the peptides specifically bound to freshly isolated type II alveolar epithelial cells compared with Hep2 cells. The results suggest that the airway phage display approach could be exploited for analyzing the molecular diversity in the lower respiratory tract.


Drug resistance biomarker ABCC4 of selinexor and immune feature in multiple myeloma.
The treatment of relapse or refractory multiple myeloma (RRMM) is still a big challenge in clinic. Recently, several clinical trials indicated that the XPO1 inhibitor, selinexor could significantly improve the remission rate in MM patients. However, the heterogeneous genetic background greatly influenced the efficiency of selinexor among MM. Here, we tried to characterized the biomarkers associated with selinexor sensitivity by analyzing gene expression data in MM patients. We found the cytogenetic background of selinexor sensitive MM patients was not limited to specific cytogenetic subtypes. In addition, by weighted gene co-expression network analysis (WGCNA), we obtained 10 key genes which showed a strong correlation with the selinexor sensitivity in MM patients. Notably, ABCC4 (MRP4) was the only gene which was both differentially expressed and proved to be clinical prognostic valuable (both for event-free survival and overall survival) in MM patients. We further validated the heterogenous expression of ABCC4 in MM cell lines and its value as a novel indicator for selinexor sensitivity. Moreover, immune infiltration analysis showed that ABCC4 expression had a significantly positive correlation with NK infiltration as well as immunotherapy target TIM-3 (HAVCR2) expression. Collectively, our findings indicated that ABCC4 might be a predictive biomarker of selinexor sensitivity in MM patients, which could be enhanced if combined with immunotherapy drugs such as TIM-3 inhibitor.


A Giant Urachal Accessory Spleen: Case Report.
Accessory spleen (AS) refers to single or multiple splenic tissues which appear outside the relative normal spleen position results from embryonic dysplasia similar in structure and function to the spleen. AS is frequently observed in the splenic hilus and or adjacent to the tail of pancreas, and only a few cases occurred in the pelvic cavity. We present an extremely rare AS case in urachus, which was initially considered as an urachal neoplasm revealed on CT images with big mass. However, the postoperative pathology confirmed it was an AS that had not been reported at urachal before. Urachal AS can be misdiagnosed as a tumor, so it is vital to make an accurate imaging preoperative diagnosis to avoid unnecessary biopsy and surgery.


[Comparative pharmacological analysis of the mechanisms of thrombocyte aggregation induced by bacterial toxins and ADP].
It has been demonstrated in experiments in vitro that exotoxin and endotoxin of Shigella sonnei produce the concentration-dependent rabbit platelet aggregation. Acetylsalicylic acid and theophylline substantially inhibit the ADP-induced aggregation and suppress to a less degree the effects of bacterial toxins. Monoiodine acetate inhibits aggregation induced by ADP and potentiates the aggregating action of toxins.