Similarity in loudness and distortion product otoacoustic emission input/output functions: implications for an objective hearing aid adjustment.
The aim of the present study was to compare distortion product otoacoustic emissions (DPOAEs) to loudness with regard to the potentiality of DPOAEs to determine characteristic quantities of the cochlear-impaired ear and to derive objective hearing aid parameters. Recently, Neely et al. [J. Acoust. Soc. Am. 114, 1499-1507 (2003)] compared DPOAE input/output functions to the Fletcher and Munson [J. Acoust. Soc. Am. 5, 82-108 (1933)] loudness function finding a close resemblance in the slope characteristics of both measures. The present study extended their work by performing both loudness and DPOAE measurements in the same subject sample, and by developing a method for the estimation of gain needed to compensate for loss of cochlear sensitivity and compression. DPOAEs and loudness exhibited similar behavior when plotted on a logarithmic scale and slope increased with increasing hearing loss, confirming the findings of Neely et al. To compensate for undesired nonpathological impacts on the magnitude of DPOAE level, normalization of DPOAE data was implemented. A close resemblance between gain functions based on loudness and normalized DPOAE data was achieved. These findings suggest that DPOAEs are able to quantify the loss of cochlear sensitivity and compression and thus might provide parameters for a noncooperative hearing aid adjustment.


Effects of Hg(II) exposure on MAPK phosphorylation and antioxidant system in D. melanogaster.
The heavy metal mercury is a known toxin, but while the mechanisms involved in mercury toxicity have been well demonstrated in vertebrates, little is known about toxicological effects of this metal in invertebrates. Here, we present the results of our study investigating the effects associated with exposure of fruit fly Drosophila melanogaster to inorganic mercury (HgCl2 ). We quantify survival and locomotor performance as well as a variety of biochemical parameters including antioxidant status, MAPK phosphorylation and gene expression following mercury treatment. Our results demonstrate that exposure to Hg(II) through diet induced mortality and affected locomotor performance as evaluated by negative geotaxis, in D. melanogaster. We also saw a significant impact on the antioxidant system including an inhibition of acetylcholinesterase (Ache), glutathione S-transferase (GST) and superoxide dismutase (SOD) activities. We found no significant alteration in the levels of mRNA of antioxidant enzymes or NRF-2 transcriptional factor, but did detect a significant up regulation of the HSP83 gene. Mercury exposure also induced the phosphorylation of JNK and ERK, without altering p38(MAPK) and the concentration of these kinases. In parallel, Hg(II) induced PARP cleavage in a 89 kDa fragment, suggesting the triggering of apoptotic cell death in response to the treatment. Taken together, this data clarifies and extends our understanding of the molecular mechanisms mediating Hg(II) toxicity in an invertebrate model.


Predictive Ability of Preoperative PT-INR and Postoperative MCP1 for Post-hepatectomy Liver Failure.
We sought a diagnostic tool using perioperative variables that might predict post-hepatectomy liver failure (PHLF). In 68 patients undergoing major hepatectomy, data on inflammatory markers and coagulation factors were prospectively collected and were compared between patients with International Study Group of Liver Surgery definition grade B/C PHLF (LF group) and those without LF (non-LF group). Preoperatively, the LF group (n=9; 13.2%) had a lower platelet count and a disintegrin-like and metalloproteinase with thrombospondin type 1 motifs 13 (ADAMTS13) activity and a higher prothrombin time-International Normalized Ratio (PT-INR) than the non-LF group. On postoperative day 1, the LF group had significantly higher serum interleukin 6 (IL6), C-C motif chemokine ligand 2 (CCL2), and IL10 levels than the non-LF group. The logistic regression model that included preoperative PT-INR and CCL2 on postoperative day 1 predicted grade B/C PHLF with 100% sensitivity and 89.8% specificity. Our findings suggest that the combination of preoperative PT-INR and CCL2 on postoperative day 1 can predict PHLF earlier and precisely after major hepatectomy.


[Hypolipidemic effect of gevilon].
The drug gevilon that produces hypolipidemic effects has been clinically tested. The drug was used to treat 53 patients suffering from coronary heart disease, hypertensive disease with severe lipid metabolic disturbances. Gevilon has been found to have a hypolipidemic effect in reducing the levels of total cholesterol, beta-cholesterol, triglycerides, increasing alpha-cholesterol levels and normalizing the atherogenicity coefficient. The hypolipidemic effect of the drug is the most pronounced in Type IIb dyslipoproteinemia. Gevilon is well tolerated by patients, it can be used in combination with the drugs given in the complex therapy for coronary heart disease and hypertension.


Age-dependent glucose tolerance in young rats under normal conditions and under glucocorticoid administration.
The dynamics of rapid intravenous glucose tolerance in 15-, 20- and 25-day-old young Wistar rats was studied under basal conditions as well as under hydrocortisone hemisuccinate administration (0.5 mg/100 g, b.w., i.p.). It was found that in basal conditions the rate of glucose assimilation increased with the age of animals. On the other hand, a parallelism between age and the rapid antiinsulin effect of hydrocortisone upon the glucose tolerance was revealed. The conclusion was drawn that the age of baby rats plays a major conditioning role in the rapid antiinsulin effect of glucocorticoid excess in the assimilation of blood glucose.


Spontaneous occurrence of synergistic bacterial gangrene following external pelvic irradiation.
A case of spontaneous synergistic bacterial gangrene occurring after external pelvic irradiation is presented in a 25-year-old woman with invasive cervical cancer. Treatment consisted of aggressive antibiotic therapy and extensive excision and debridement followed by split-thickness skin grafting. Both recovery and cosmetic results were satisfactory. The pathophysiology, predisposing factors, and treatment modalities are presented.


The association between physical activity and atrial fibrillation applying the Heaviside function in survival analysis: the Multi-Ethnic Study of Atherosclerosis.
Although the effect of physical activity (PA) on the incidence of atrial fibrillation (AF) has been studied, contradictory results have been reported. Such discrepancies may reflect the different effects of various types of PA upon AF, as well as gender interactions. Therefore, we aimed to evaluate the associations of PA types (total, moderate/vigorous, and intentional), as well as walking pace, with AF risk in men and women. Using the Multi-Ethnic Study of Atherosclerosis Typical Week Physical Activity Survey, 3 PA measures and walking pace were calculated among 6,487 men and women aged 45-84 years. The incidence of AF over approximately 11 years of follow-up was ascertained. The association of each PA measure and walking pace with AF incidence was estimated using multivariable Cox proportional hazard models. An extended Cox model with Heaviside functions (hv) of time was used to estimate the effects of time-varying covariates. During 11 years of follow-up (49,557 person-years), 242 new AF cases occurred. The incidence rate of AF was 48.83 per 10,000 person-years. The proportional hazard (PH) assumption for total PA among women was not met; hence, we used the hv to calculate the hazard ratio. Total PA in women in the hv2 analysis was negatively associated with AF in all 3 models, although for hv1 no significant association was observed. The PH assumption for walking pace among men was not met, and none of the hv showed a statistically significant association between walking pace and AF in men. These results suggest that PA is inversely associated with AF in women.


Intracellular calcium-dependent regulation of the sperm-specific calcium-activated potassium channel, hSlo3, by the BKCa activator LDD175.
Plasma membrane hyperpolarization associated with activation of Ca2+-activated K+ channels plays an important role in sperm capacitation during fertilization. Although Slo3 (slowpoke homologue 3), together with the auxiliary γ2-subunit, LRRC52 (leucine-rich-repeat-containing 52), is known to mediate the pH-sensitive, sperm-specific K+ current KSper in mice, the molecular identity of this channel in human sperm remains controversial. In this study, we tested the classical BKCa activators, NS1619 and LDD175, on human Slo3, heterologously expressed in HEK293 cells together with its functional interacting γ2 subunit, hLRRC52. As previously reported, Slo3 K+ current was unaffected by iberiotoxin or 4-aminopyridine, but was inhibited by ~50% by 20 mM TEA. Extracellular alkalinization potentiated hSlo3 K+ current, and internal alkalinization and Ca2+ elevation induced a leftward shift its activation voltage. NS1619, which acts intracellularly to modulate hSlo1 gating, attenuated hSlo3 K+ currents, whereas LDD175 increased this current and induced membrane potential hyperpolarization. LDD175-induced potentiation was not associated with a change in the half-activation voltage at different intracellular pHs (pH 7.3 and pH 8.0) in the absence of intracellular Ca2+. In contrast, elevation of intracellular Ca2+ dramatically enhanced the LDD175-induced leftward shift in the half-activation potential of hSlo3. Therefore, the mechanism of action does not involve pH-dependent modulation of hSlo3 gating; instead, LDD175 may modulate Ca2+-dependent activation of hSlo3. Thus, LDD175 potentially activates native KSper and may induce membrane hyperpolarization-associated hyperactivation in human sperm.


In situ source zone sediment mixing coupled to groundwater biostimulation to enhance phenol natural attenuation.
Phenol is an industrially key compound that has a wide range of applications and also one of the most commonly found toxic pollutants in wastewaters and groundwater. This paper demonstrates the applicability of in situ remediation at a deactivated industrial site using source zone excavation and sediment mixing associated with nutrients delivery into groundwater. Sediment excavation and mixing displaced the entrapped source zone enhancing mass transfer into groundwater and contaminant bioavailability. A nutrient solution prepared with nitrate, phosphate, sodium hydroxide and hydrogen peroxide was continuously delivered into groundwater to stimulate biodegradation and restrict plume migration. The observed correlation between phenol-dependent Enterobacteriaceae concentrations throughout the remediation time frame supported circumstantial evidence of biodegradation. Phenol concentration in groundwater (up to 1,300 mg/L) was reduced >99% after 5 months following remediation and remained under the established site specific target level (4 mg/L). Nitrate and phosphate concentrations returned to background concentrations levels at the end of the remediation. Overall, the proposed in situ remediation scheme was effective to remediate this particular aquifer contaminated with phenol for over 20 years.


Risk factors for developing thyroid-associated ophthalmopathy among individuals with Graves disease.
Thyroid-associated ophthalmopathy (TAO) is a common and debilitating manifestation of Graves disease (GD). Presently little is known about factors that may increase the risk of developing TAO among patients with GD. To identify risk factors associated with the development of TAO among individuals with newly diagnosed GD. In this longitudinal cohort study, all beneficiaries 18 years of age or older with newly diagnosed GD who were continuously enrolled in a large nationwide US managed care network and who visited an eye care professional 1 or more times from 2001 to 2009 were identified. International Classification of Diseases, Ninth Revision, Clinical Modification billing codes were used to identify those who developed manifestations of TAO. Multivariable Cox regression was used to determine the hazard of developing TAO among persons with newly diagnosed GD, with adjustment for sociodemographic factors, systemic medical conditions, thyrotropin levels, and medical and surgical interventions for management of hyperthyroidism. Manifestations of TAO measured by hazard ratios (HRs) with 95% CIs. Of 8404 patients with GD who met the inclusion criteria, 740 (8.8%) developed TAO (mean follow-up, 374 days since initial GD diagnosis). After adjustment for potential confounders, surgical thyroidectomy, alone or in combination with medical therapy, was associated with a 74% decreased hazard for TAO (adjusted HR, 0.26 [95% CI, 0.12-0.51]) compared with radioactive iodine therapy alone. Statin use (for ≥60 days in the past year vs <60 days or nonuse) was associated with a 40% decreased hazard (adjusted HR, 0.60 [CI, 0.37-0.93]). No significant association was found for the use of nonstatin cholesterol-lowering medications or cyclooxygenase 2 inhibitors and the development of TAO. If prospective studies can confirm our finding that a thyroidectomy and statin use are associated with substantially reduced hazards for TAO among patients with GD, preventive measures for this burdensome manifestation of GD may become a reality.


CaGdF5 based heterogeneous core@shell upconversion nanoparticles for sensitive temperature measurement.
Lanthanide-doped upconversion nanoparticles (UCNPs) have attracted great attention in temperature sensing because of their widespread thermal quenching effect (TQE), a phenomenon in which luminescence intensity decreases as the temperature increases. However, enhancing the TQE of activated ions without changing the dopants or the host is still challenging. Herein, Yb3+ and Er3+ codoped UCNPs in a cubic CaGdF5 host were synthesized by a coprecipitation method for optical temperature sensing. Compared with the homogeneous shell (CaGdF5), those heterogeneous (CaF2) shelled UCNPs exhibited stronger upconversion luminescence (UCL) due to the significantly reduced multiphonon nonradiative relaxation. Further, we investigated the effects of homogeneous and heterogeneous shells on TQE. The relationship between the intensity ratio of the green emission bands of Er3+ ions (2H11/2 → 4I15/2 and 4S3/2 → 4I15/2) and temperature are obtained for these two core@shell UCNPs. The results demonstrated that the UCNPs with CaF2 shells are more sensitive to temperature in the 200-300 K. The maximum thermal sensitivity of CaGdF5:Yb,Er@CaF2 could reach 2.2% K-1 at 200 K. These results indicate that the heterogeneous core@shell UCNPs are promising for use as optical temperature sensors.


Two metabolic pathways of tetrahydronorharmane (tetrahydro-beta-carboline) in rats.
Metabolites of (14C) tetrahydronorharmane (THN, tetrahydro-beta-carboline) have been identified by mass spectrometry and nuclear magnetic resonance spectroscopy. Two metabolic pathways are suggested: Hydroxylation of the benzene ring--most probably with an epoxide as intermediate--though no hydroxylated THN could be detected in the urine samples of male and female rats but conjugated compounds as the main metabolites. The intermediary epoxide is supported by the fact, that the hydroxy substituent of THN is positioned on C-6 or C-7 with a ratio of 55:45 in female rats and of 45:55 in male rats. Dehydrogenation yielding norharmane. This substance possibly gives rise to another metabolite--1,2-dihydro-beta-carboline-1-one. The pharmacological and toxicological implications of these findings are discussed.


Direct mapping of ligandable tyrosines and lysines in cells with chiral sulfonyl fluoride probes.
Advances in chemoproteomic technology have revealed covalent interactions between small molecules and protein nucleophiles, primarily cysteine, on a proteome-wide scale. Most chemoproteomic screening approaches are indirect, relying on competition between electrophilic fragments and a minimalist electrophilic probe with inherently limited proteome coverage. Here we develop a chemoproteomic platform for direct electrophile-site identification based on enantiomeric pairs of clickable arylsulfonyl fluoride probes. Using stereoselective site modification as a proxy for ligandability in intact cells, we identify 634 tyrosines and lysines within functionally diverse protein sites, liganded by structurally diverse probes. Among multiple validated sites, we discover a chiral probe that modifies Y228 in the MYC binding site of the epigenetic regulator WDR5, as revealed by a high-resolution crystal structure. A distinct chiral probe stimulates tumour cell phagocytosis by covalently modifying Y387 in the recently discovered immuno-oncology target APMAP. Our work provides a deep resource of ligandable tyrosines and lysines for the development of covalent chemical probes.


Novel lactotransferrin-derived synthetic peptides suppress cariogenic bacteria in vitro and arrest dental caries in vivo: [Novel lactotransferrin-derived anticaries peptides].
Objectives: The aim of the study was to design and synthesise novel lactotransferrin-derived antimicrobial peptides (AMPs) with enhanced antibacterial activity against cariogenic bacteria. Methods: We obtained the LF-1 (WKLLRKAWKLLRKA) and LF-2 (GKLIWKLLRKAWKLLRKA) AMPs, based on the N-terminal functional sequence of lactotransferrin, and characterised their physicochemical properties and secondary structure. Their antibacterial activity against caries-associated bacteria was evaluated using bacterial susceptibility and time-killing assays, as well as transmission electron microscopy (TEM). The antibiofilm activity against Streptococcus mutans biofilms was determined using biofilm susceptibility assays and confocal laser scanning microscopy (CLSM). A rodent model of dental caries was adopted to evaluate their anticaries effectiveness in vivo. Results: Both peptides possessed an α-helical structure with excellent amphipathicity. LF-1 was effective against S. mutans and Actinomyces species, whereas LF-2 showed more potent antibacterial activity than LF-1 against a broader spectrum of tested strains. Both peptides inhibited the formation of S. mutans biofilm starting at 8 μmol/L and exerted effective eradication of S. mutans in preformed biofilms. Both peptides exhibited satisfactory biocompatibility and exerted significant anticaries effects in a rodent model. Conclusion s: Both lactotransferrin-derived peptides displayed strong antimicrobial activity against cariogenic bacteria and S. mutans biofilm in vitro and effectively inhibited dental caries in vivo.


Polymyoclonus, ventricular fibrillation and Takotsubo after accidental spinal injection of tranexamic acid.
Several factors have been identified as contributing to medication administration errors, including look-alike, sound-alike (LASA) errors. LASA errors are important causes of serious adverse events arising from spinal injection of tranexamic acid, which can be confused with ampoules of local anaesthesia.We present a case of accidental injection of 250 mg of tranexamic acid rather than prilocaine during spinal anaesthesia. The patient developed lower extremities myoclonus, followed by generalised convulsions and ventricular fibrillation, that was reverted within 6 min. Severe cardiogenic shock requiring both inotropic and vasopressor therapy followed, along with a classic apical ballooning pattern on echocardiography and elevated myocardial injury markers, indicating Takotsubo cardiomyopathy. The patient's condition progressively improved to full recovery, and she was discharged from hospital after 1 month with no neurological deficit or cardiac dysfunction.To our knowledge, this is the 28th reported case of accidental spinal injection of tranexamic acid. We present a brief review of previously published cases.


Protective role of curcumin in oxidative stress of breast cells.
Curcumin (diferuloylmethane) is a well known antioxidant that exerts anti-proliferative and apoptotic effects. The effects of curcumin were evaluated in a breast cancer model that was developed with the immortalized breast epithelial cell line, MCF-10F after exposure to low doses of high LET (linear energy transfer) α particles (150 keV/µm) of radiation, and subsequently cultured in the presence of 17β-estradiol (estrogen). This model consisted of human breast epithelial cells in different stages of transformation: i) a control cell line, MCF-10F, ii) an estrogen-treated cell line, named Estrogen, iii) a malignant cell line, named Alpha3 and iv) a malignant and tumorigenic, cell line named Alpha5. Curcumin decreased the formation of hydrogen peroxide in the control MCF-10F, Estrogen and Alpha5 cell lines in comparison to their counterparts. Curcumin had little effect on NFκB (50 kDa) but decreased the protein expression in the Estrogen cell line in comparison to their counterparts. Curcumin enhanced manganese superoxide dismutase (MnSOD) protein expression in the MCF-10F and Alpha3 cell lines. Results indicated that catalase protein expression increased in curcumin treated-Alpha3 and Alpha5 cell lines. Curcumin slightly decreased lipid peroxidation in the MCF-10F cell lines, but significantly (P<0.05) decreased it in the Alpha5 cell line treated with curcumin in comparison to their counterparts as demonstrated by the 8-iso-prostaglandin F2α (8-iso-PGF2α) levels. It can be concluded that curcumin acted upon oxidative stress in human breast epithelial cells transformed by the effect of radiation in the presence of estrogen.


Substrate-Controlled Three-Component Synthesis of Diverse Fused Heterocycles.
A chemoselective strategy toward a variety of fused heterocyclic scaffolds relying on a three-component condensation of heterocyclic ketene aminals (HKAs) or corresponding thioaminals with aryl glyoxals and cyclic 1,3-dicarbonyl compounds has been developed and explored. Depending on the applied combination of substrates, the strategy can be tuned to provide straightforward access to imidazo[1,2-a]quinoline, pyrrolo[1,2-a]imidazole, and pyrrolo[2,1-b]thiazole frameworks.


Exogenous GABA is quickly metabolized to succinic acid and fed into the plant TCA cycle.
Exogenous application of γ-aminobutyric acid (GABA) could improve plant tolerance to environmental stresses such as hypoxia, heat, cold, drought, and salt stress. However, the mechanism by which GABA relieves stress is poorly understood. Here, we studied the uptake and metabolism of exogenous GABA in citrus leaves. Leaves were incubated in GABA solutions and the levels of endogenous GABA, succinic acid, and fumaric acid were investigated. Interestingly, the levels of endogenous GABA, succinic acid, and fumaric acid were quickly increased in GABA-treated leaves. This result indicated that GABA was taken up by the leaf, metabolized to succinic acid, and fed into the tricarboxylic acid cycle (TCA). This finding suggested that exogenous GABA could enhance plant resistance to biotic and abiotic stresses by generating more energy through the activation of the GABA shunt pathway and TCA cycle.


Impact of heavy pruning on development and photosynthesis of Tilia cordata Mill. trees.
Tree pruning is carried out to reduce conflict with infrastructure, buildings, and any other human activity. However, heavy pruning may result in a diminished tree crown capacity for sugar production and exposure to fungal infection. This risk leads to a decrease in tree stability or vigour. In this work, we analysed the effect of heavy pruning of roadside trees on the photosynthetic performance process compared to neighbouring unpruned trees. Four years of tree crown growth was studied by terrestrial imaging. Tree vitality (Roloff's classification) and risk (Visual Tree Assessment) were evaluated. Over-pruned trees showed intensified photosynthetic efficiency during the growing season following pruning. Particularly ET0/TR0 and PIABS tended to increase in pruned trees while higher Fv/Fm was noted only in late October, suggesting delayed leaf senescence. After four years, pruned trees rebuilt their crowns, however not in their entirety. Results obtained from biometric, vitality, and risk assessment showed high differentiation in pruned tree crown recovery. Our results revealed that despite the intensified efforts of trees to recover from wounding effects, severe pruning evokes dieback occurrence and a higher risk of failure in mature trees.


Dinucleotide codon-anticodon interaction as a minimum requirement for ribosomal aa-tRNA binding: stabilisation by viomycin of aa-tRNA in the A site.
The requirements for the decoding process at the ribosomal A site have been investigated in the presence of viomycin. For these studies natural mRNA was replaced either by the synthetic oligonucleotide A-U-G(-U)n, with 0 less than or equal to n less than or equal to 4, or by a physical mixture of the oligonucleotides A-U-G and various oligo(U) sequences. Thus the effect of the "removal" of selected covalent bonds from the sequence A-U-G(U)n could be studied. When the ribosomal P site contains tRNAMetf, then normally the full hexanucleotide "messenger" A-U-G-U-U-U is needed for the EF-Tu-mediated binding of Phe-tRNA into the A site. However in presence of viomycin the pentanucleotide A-U-G-U-U suffices for this. It is also possible in the presence of viomycin to replace A-U-G-U and U-U. In all the above systems the binding of Phe-tRNA required the presence of EF-Tu and GTP. The results suggest that viomycin reinforces interactions between aa-tRNA and the A site after the codon-anticodon recognition step.


Immune Signatures and Survival of Patients With Metastatic Melanoma, Renal Cancer, and Breast Cancer.
Despite remarkable recent progress in treating solid cancers, especially the success of immunomodulatory antibody therapies for numerous different cancer types, it remains the case that many patients fail to respond to treatment. It is therefore of immense importance to identify biomarkers predicting clinical responses to treatment and patient survival, which would not only assist in targeting treatments to patients most likely to benefit, but might also provide mechanistic insights into the reasons for success or failure of the therapy. Several peripheral blood or tumor tissue diagnostic and predictive biomarkers known to be informative for cancer patient survival may be applicable for this purpose. The use of peripheral blood ("liquid biopsy") offers numerous advantages not only for predicting treatment responses at baseline but also for monitoring patients on-therapy. Assessment of the tumor microenvironment and infiltrating immune cells also delivers important information on cancer-host interactions but the requirement for tumor tissues makes this more challenging, especially for monitoring sequential changes in the individual patient. In this contribution, we will review our findings on immune signatures potentially informative for clinical outcome in melanoma, breast cancer and renal cell carcinoma, particularly the outcome of checkpoint blockade, by applying multiparametric flow cytometry and mass cytometry, routine clinical monitoring and functional testing for predicting and following individual patient responses to therapy.


Clonal analysis of T lymphocytes in spleens from patients with Hodgkin's disease. Frequent occurrence of unusual T4-positive cells which co-express cytolytic activity and production of interleukin-2.
T-lymphocyte populations isolated from spleens of untreated patients with Hodgkin's disease (HD) were grown by combining limiting dilution techniques and an assay system that allows clonal proliferation of virtually all human T cells. Under these conditions, high proportions of splenic T lymphocytes (50-80%) underwent clonal expansion, so that the set of clones obtained could be considered representative of the starting T-cell population. A total number of 229 clones from 6 HD spleens (3 uninvolved and 3 histologically involved by the disease) and 133 clones from 3 control spleens (obtained from otherwise healthy individuals, who underwent post-traumatic splenectomy) were examined for surface markers and tested in functional assays. One hundred and seventy-five clones from HD spleens and 75 clones from control spleens expressed the "helper/inducer" (T3+ T4+ T8-)phenotype, whereas as 54 clones from HD spleens and 58 control clones expressed the "cytotoxic/suppressor" (T3+T4-T8+) phenotype. As assessed by a non-specific lectin-dependent lytic assay, the proportion of HD clones displaying cytolytic activity was higher than that of cytolytic clones derived from control spleens. The majority of T4+ clones obtained from HD spleens (either uninvolved or histologically involved by the disease) were cytolytic, whereas only a small proportion (less than 10%) of T4+ clones derived from normal peripheral blood or spleens displayed cytolytic activity. The cytolytic potential of T4+ clones obtained from HD spleens did not reflect the activity of natural killer (NK) cells, since a minority of these clones exerted NK activity on K562 target cells. In addition, most of the T4+ cytolytic clones derived from HD spleens produced particularly high amounts of interleukin-2 (IL-2). These data indicate that T lymphocytes which concentrate in spleens of patients with HD consist at least in part of an infrequent T4+ cell subset co-expressing cytolytic activity and production of IL-2. These cells may reflect a cytotoxic reaction against unknown antigens associated with self class-II histocompatibility antigens.


Latent profiles of ethical climate and nurses' service behavior.
Hospital ethical climate has important implications for clinical nurses' service behavior; however, the relationships are complicated by the fact that five types of ethical climate (caring, law and code, rules, instrumental, and independence) can be combined differently according to their level and shape differences. Recent developments in person-centered methods (e.g., latent profile analysis (LPA)) have helped to address these complexities. From a person-centered perspective, this study explored the distinct profiles of hospital ethical climate and then examined the relationships of the profiles with clinical nurses' service behavior (both in-role and extra-role service behavior). A quantitative study was conducted using cluster random sampling. Latent profile analysis and binary coded hexadecimal (BCH) analysis were conducted using Mplus 8.2. A total of 871 clinical nurses in China were surveyed using the Ethical Climate Scale and Nurses' Service Behavior Questionnaire. Ethical approval was obtained from the IRB of the First Affiliated Hospital of Jinan University (No. KY-2020-090). A four-profile hospital ethical climate model provided the best fit for the data. The four different profiles not only varied in level, but also in shape: high normative and low egoism (45.8%), high ethical climate (19.9%), low ethical climate (3.6%), and moderate ethical climate (30.8%). These profiles differentially predicted clinical nurses' overall, in-role, and extra-role service behaviors. The results reveal new insights into the nature of hospital ethical climate and how different clinical nurses in these profiles can be best managed to accomplish different forms of service behavior.


[Metastatic tumors of the retroperitoneal space].
In 22 patients retroperitoneal nonorganic tumors, considered to be primary, proved to be metastatic. Prior to surgery the character of neoplasms was recognized only in 4 patients. Due to unwarranted efforts of "radical" removal of tumors 2 of 4 patients died. In 3 cases neoplasms were urgently removed due to internal hemorrhage and obstruction. In 7 cases a palliative effect of radiotherapy. 5-fluoruracil thiophosphamide employed prior to detection of the primary focus, was obtained. The latter was found following 3-12 months in the stomach (1), small intestine (1) and rectum (4), kidneys (4) and genitalia (9) in further follow-up of patients.


Surgical outcome in superficially spreading early gastric cancer.
Superficially spreading early gastric cancer is characterized by wide horizontal extension without deep vertical invasion. This study aimed to clarify the clinicopathological characteristics and prognosis of this rare disease. We defined superficially spreading early gastric cancer as any tumor invading the submucosal layer that measured > or =60 mm in diameter. The clinicopathological characteristics and results of surgery were compared between 60 patients with superficially spreading tumors and 621 patients with the common type (<60 mm in diameter). For superficially spreading cancers,significantly higher numbers of female patients, undifferentiated and scirrhous types, infiltrating growth and lymph node metastases were seen. The number of metastatic lymph nodes was greater than in the common type. There was no significant difference in the distribution of metastatic lymph nodes between the two groups. For superficially spreading tumors, wide gastrectomy with extended lymph node dissection was frequently employed. Lymph node metastasis, but not tumor diameter, was a prognostic factor in uni- and multivariate analyses. Although superficially spreading early gastric cancer has histologically distinct properties, gastrectomy with lymph node dissection with sufficient surgical margin could be a suitable treatment.


Determination of rat oral bioavailability of soy-derived phytoestrogens using an automated on-column extraction procedure and electrospray tandem mass spectrometry.
In recent years, consumption of herbal supplements as an alternative to pharmaceutical drug therapy has increased. For example, with the health claims labeling which describes the link between soy-protein and a reduced risk of coronary heart disease (CHD), the consumption of soy and soy-derived phytoestrogens has increased dramatically. That being said, the oral bioavailability of only a few soy phytoestrogens such as Daidzein and Genestein have been previously estimated. In this paper, we present the calculated percent of rat oral bioavailability of five soy-derived phytoestrogens (Genistein, Daidzein, Biochanin A, Coumestrol, and Zearalenone) in male Sprague-Dawley rats. The plasma quantitation required for the bioavailability calculation is performed by using a rapid on-line plasma extraction procedure for the quantitative analysis. To further speed up the analysis the rats were dosed using the 'n-in-one' (cassette) protocol. The rapid on-line extraction/quantitation methodology coupled to the cassette dosing analysis of phytoestrogens is the key point of this paper. The limit of quantitation (LOQ) for each compound was 1-1000 ng/ml with each plasma sample analysis taking less than 2 min. In general the percent oral bioavailability was determined to be between 11 and 28%.


Effectiveness of prednisolone during phenytoin therapy.
The effects of diphenylhydantoin (DPH) on the clearance of prednisolone from plasma, its bioavailability, and its biologic effectiveness were studied in 5 persons before and after daily DPH therapy for more than 3 wek. DPH decreased the mean half-time of disappearance of prednisolone from plasma by 45% and increased its metabolic clearance rate by an average of 77%. The gastrointestinal absorption of prednisolone and its first-pass clearance through splanchnic tissues were not significantly altered by DPH. The mean oral midnight dose of prednisolone required to suppress the 8 A.M. plasma level of cortisol to 5 microgram/dl was doubled following treatment of DPH. The increment in dose of prednisolone varied from 58% to 260% in the five individuals.


[Neuroendocrine and immunological interactions in chronic alcoholism].
The levels of neuromediators, neurohormones and the parameters of cellular and humoral immunity in 100 patients suffering from chronic alcoholism were studied before and after the use of the corresponding stimulants and blockers of these biological systems. The pathogenetic significance of disturbed interactions of the neuroendocrine and immune systems in chronic alcoholism was established. The ways of search for means of treating alcoholism are determined.


High-grade endometrial stromal sarcoma: clinicopathologic and immunohistochemical study of a case.
This report describes a case of high-grade stromal sarcoma occurring in a 53-year-old woman. Preoperative and pathologic findings showed up a large tumoral nodule confined to the uterus. The patient underwent a total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy and dissection of pelvic and para-aortic lymph-nodes; successively she underwent pelvic and abdominal radiotherapy and chemotherapy, which was discontinued because of leukopenia. Histologically the tumor was made up of cells resembling endometrial stromal cells with only mild cytologic atypia and had up to 24 mitoses x 10 HPF in the most cellular areas. Immunohistochemically it showed a diffuse positivity for vimentin and a focal positivity for muscular actin and desmin. The patient died of this disease nine months postoperatively. These features underline that a uterine sarcoma with histological features similar to a low-grade endometrial stromal sarcoma but with high mitotic rate may behave as a very aggressive tumor even when diagnosed at the initial stage; the immunohistochemical data indicate that these tumors may show smooth-muscle differentiation.


Identification of the activating and conjugating enzymes of the NEDD8 conjugation pathway.
NEDD8 is a ubiquitin-like molecule that can be covalently conjugated to a limited number of cellular proteins, such as Cdc53/cullin. We have previously reported that the C terminus of NEDD8 is efficiently processed to expose Gly-76, which is required for conjugation to target proteins. A combination of data base searches and polymerase chain reaction cloning was used to identify a cDNA encoding human UBA3, which is 38% identical to the yeast homologue, 22% identical to human UBA2, and 19% identical to the C-terminal region of human UBE1. The human UBA3 gene is located on chromosome 3p13 and gave rise to a 2.2-kilobase pair transcript that was detected in all tissues. Human UBA3 could be precipitated with glutathione S-transferase (GST)-NEDD8, but not with GST-ubiquitin or GST-sentrin-1. Moreover, human UBA3 could form a beta-mercaptoethanol-sensitive conjugate with NEDD8 in the presence of APP-BP1, a protein with sequence homology to the N-terminal half of ubiquitin-activating enzyme. We have also cloned human UBC12 and demonstrated that it could form a thiol ester linkage with NEDD8 in the presence of the activating enzyme complex. Identification of the activating and conjugating enzymes of the NEDD8 conjugation pathway should allow for a more detailed study of the role of NEDD8 modification in health and disease.


Partially hydrolyzed guar gum is associated with improvement in gut health, sleep, and motivation among healthy subjects.
Partially hydrolyzed guar gum dietary fiber is well recognized for a number of health benefits. In the present study, we aim to investigate the effects of partially hydrolyzed guar gum on constipation, intestinal microbiota as well as mental health in healthy subjects. In the randomized, parallel, double-blind, and placebo-controlled study the enrolled healthy men and women volunteers took either 3 g/day (T3) or 5 g/day (T5) of dietary fiber intakes for eight consecutive weeks compared to placebo (T0). The fecal characteristics, fecal microbiota, defecation characteristics, and quality of life (QOL) questionnaire were investigated. The results revealed a significant suppression in fecal potent harmful mucolytic bacteria in the T3 and T5 groups compared to the T0 group. The defecation frequency, excretory feeling, and scores of sleep and motivation questionnaire were also improved in the dietary fiber intake groups, showing a significant difference in the T5 group compared to the T0 group. In summary, the consumption of partially hydrolyzed guar gum dietary fiber is found effective in suppressing the potent harmful mucolytic bacteria that could be associated with the improvement of constipation-related symptoms including mental health in terms of sleep and motivation among the healthy subjects.


Gender as a determinant of physical activity levels and mental health of medical students from Poland and Belarus in the context of the COVID-19 pandemic.
COVID-19 pandemic has brought about unfavourable changes regarding both physical activity (PA) levels and patterns of behaviour associated with mental health. The study sought to assess PA levels and kinesiophobia in medical students from Poland and Belarus taking account of gender. A total of 779 students (405 students from University of Grodno (UG), Belarus, and 374 students from John Paul II University of Applied Sciences (ABNS) in Biala Podlaska, Poland) took part in the study. Women constituted 74.2% of the study population. A diagnostic survey as well as two research tools, i.e., the International Physical Activity Questionnaire (IPAQ)-short form, and the Tampa Scale for Kinesiophobia (TAMPA) were employed in the study. Students from ABNS manifested significantly higher levels of PA. Taking into account gender, male respondents displayed significantly higher levels of MET-min/week (MET-metabolic equivalent of task). As for kinesiophobia, significantly higher levels were demonstrated by students from UG. Its higher levels were also noted among women. The findings of the study did not reveal strong correlations between kinesiophobia and PA levels in students from Poland and Belarus in the context of different approaches to the pandemic that both countries adopted. Students from ABNS proved to be more physically active. In turn, participants from UG exhibited significantly higher levels of kinesiophobia. Gender was the factor that significantly differentiated levels of kinesiophobia, with women displaying its higher levels.


Effect of exercise on calf muscle pump function in patients with chronic venous disease.
Musculoskeletal dysfunction may be associated with poor calf muscle pump function in patients with chronic venous ulceration. The aim of this study was to evaluate the effects of physical exercise on calf muscle pump function. Twenty patients were recruited into a 6-week intensive exercise programme. Calf muscle function and calf muscle pump function were assessed using an isokinetic device and air plethysmography respectively, before and after the exercise programme. There was significant improvement in calf muscle pump function, measured as increased ejection fraction and decreased residual fraction (P < 0.05); however, venous reflux was not altered (P > 0.05). Calf muscle strength and endurance parameters all increased, but not significantly (P > 0.05). Poor calf muscle pump function in patients with chronic venous ulceration can be improved by physical exercise.


Synthesis of the evidence: Clinical guideline for the diagnosis and treatment of precocious puberty.
Three systematic reviews were conducted to formulate the recommendations on diagnosis, treatment and follow-up of patients with precocious puberty: interventions for the treatment of precocious puberty that included the outcomes of final or near-final height, mental health, metabolic health, health bone, or blockade success; comparative observational studies evaluating long-term outcomes in subjects with a history of precocious puberty; and diagnostic test accuracy studies for puberty.


Initial phase establishment of an in vitro method for developmental neurotoxicity test using Ki-67 in human neural progenitor cells.
Building a precise alternative neurotoxicological test is of great importance to respond to societal and ethical requirements. In this study, a new developmental neurotoxicity test (DNT) was established with the human neural progenitor cell line. ReNcell CX cells were exposed to neurotoxic chemicals (aphidicolin, hydroxyurea, cytosine arabinoside, 5-fluorouracil, and ochratoxin A) or non-neurotoxic chemicals (sodium gluconate, sodium bicarbonate, penicillin G, and saccharin). Propidium iodide (PI) was used to evaluate cell viability. BrdU and Ki-76 were employed to determine cell proliferation. Based on the cell viability and proliferation, mathematical models were built by linear discriminant analysis. Furthermore, the neurotoxic-considered chemicals inhibited cell cycle progression at the protein level, supporting the biomolecular rationale for the predictive model. Overall, these results show that the new test method can be used to determine the potential developmental neurotoxicants or new drug candidates.


Effects of high-dose major components in oral disinfectants on the cell cycle and apoptosis in primary human gingival fibroblasts in vitro.
We evaluated the effects of high-dose major components in oral disinfectants on oral cells from the standpoints of the cell cycle and apoptosis. We examined the viability and cell cycle of human gingival fibroblasts (HGFs) treated with the components of dental disinfectants, benzethonium chloride (BEC), benzalkonium chloride (BAC), and povidone iodine (PVD-I) using a cell counting kit and flow cytometry. The IC(50) inhibitory concentration value in HGF cultures at 24 hours was 1.3x10(-2) mM BEC, 6.0x10(-3) mM BAC, and 2.6x10(-1) mM PVD-I. In the cell cycle analysis, propidium iodide-stained HGFs were arrested in G(0)/G(1) of the cell cycle by all three disinfectants, and in the apoptosis assay, annexin V-FITC/PI-stained HGFs that became apoptotic at 5.0x10(-2) and 1.0x10(-1) mM BEC and 5.0x10(-2) and 1.0x10(-1) mM BAC, but not in PVD-I at concentrations as high as 5.0x10(-1) mM. Our findings describe the effects of high-dose oral disinfectants, rather than clinical concentrations. Nevertheless, appreciating the effects of high-dose disinfectants absorbed into the human body is important, where they may accumulate in specific tissues and cells.


Minimally invasive treatment of gastric gastrointestinal stromal tumors: laparoscopic and endoscopic approach.
This study aimed to verify the long-term outcome of a minimally invasive endoscopic or laparoscopic approach for the treatment of gastric gastrointestinal stromal tumor (GIST). This single-center study involved a retrospective review of gastric tumors that were pathologically confirmed as GIST. A total of 84 patients who underwent minimally invasive endoscopic or laparoscopic resection for gastric GIST were enrolled from February 2002 to June 2007. These demographics, tumor characteristics, and outcomes were analyzed for identification of outcomes and feasibility of endoscopic or laparoscopic resection. Of 84 patients, 27 and 57 patients underwent endoscopic and laparoscopic resection, respectively. The average tumor size was 3.1 ± 1.7 cm. With a mean follow-up of 40.5 ± 20.7 months, 82 (97.7%) patients were disease free. Two patients, both of whom underwent laparoscopic resection, were alive with peritoneal recurrence. Two (7.4%) and 6 (10.5%) patients, respectively, had postoperative complications after endoscopic resection and laparoscopic resection. There was no significant difference in the operative morbidity according to tumor size. There was no postoperative mortality. Laparoscopic surgery for gastric GIST is safe and feasible, even in large (>5 cm) tumors. Because endoscopic resection showed good results without recurrence, this approach can be useful in selected cases with a high operative risk or a need for preservation of organ function.


Three dimensional cyclic trinuclear units based metal-covalent organic frameworks for electrochemical CO2RR.
A three-dimensional metal-covalent organic framework (3D-MCOF) based on cyclic trinuclear units was synthesized using organic tetrahedral linkers and copper-based cyclic trinuclear complexes. The novel type of 3D-MCOF, named 3D-CTU-MCOF, with the ctn topology, is reported herein for the first time. Our study demonstrated enhanced electrocatalytic capacity for CO2 reduction reaction of 3D-CTU-MCOF compared to independent cyclic trinuclear units.


Long-term skeletal and dental effects of facemask versus chincup treatment in Class III patients : A retrospective study.
To investigate the skeletal and dental changes during chincup versus facemask treatment, to compare the long-term effects of the two appliances, and to document the impact of each on treatment success. In all, 61 patients with Class III syndrome were retrospectively analyzed at three examination times: 7.8 ± 1.7 years of age (T0, pretreatment), 9.6 ± 2.4 years of age (T1, posttreatment), and around 15-20 years later (T2, long-term follow-up). Significant changes of specific cephalometric parameters for all treatment times: T0-T1 (SNA, interbase and gonial angle, Björk's sum angle, maxillomandibular differential, and distance of upper lip to esthetic line), T1-T2 (NL-NSL, SNB, mandibular-body length, effective mandibular length, and effective maxillary length), and T0-T2 (mandibular-body length, effective mandibular length, effective maxillary length, maxillomandibular differential, SNB, ANB, gonial angle, Björk's sum angle, and Wits appraisal). The T1-T2 results illustrate that in both treatment groups the typical Class III growth pattern often reappeared after treatment, including gains in SNB angle, condylion-gnathion length, and gonion-menton distance. Either a facemask or a chincup may be effectively used to treat Class III malocclusion. There were differences in long-term stability. Maxillary development was similarly favorable in both groups of patients with successful outcome. The subgroup in whom chincup treatment had failed were mainly characterized by excessive mandibular growth, or lack of maxillary catch-up growth, with deterioration of the maxillomandibular relationship notably in the initial phase of treatment. Early chincup treatment did not have an adverse impact on the temporomandibular joints.


Biological markers in urologic cancer.
Tumor markers (TMs) play an important part in the management of urologic cancer. Alpha-fetoprotein, human chorionic gonadotropin, and occasionally lactic dehydrogenase serological determinations have become indispensable in the management of nonseminomatous germ cell testicular tumor patients, particularly after initial therapy, whereas human chorionic gonadotropin and probably placental alkaline phosphatase are important in seminoma. Prostatic acid phosphatase has long been important for the monitoring of patients with carcinoma of the prostate. The availability of the immunologic assays instead of the enzymatic assays has improved sensitivity somewhat but clinical interpretation has also become more complicated. Prostatic specific antigen is already an important tissue marker for carcinoma of the prostate and promises to be an important serological one, possibly surpassing prostatic acid phosphatase in importance. Analysis of DNA by automated flow cytometry is becoming important in the early detection and follow-up of bladder cancer patients. Studies concerning the tissue analysis of blood group antigens in bladder cancer continue to demonstrate that this approach can provide unique clinical information and interesting biological insights, but its role in routine clinical management remains to be determined. Currently, TMs have little clinical significance in renal cell carcinoma, but the availability of monoclonal antibodies to renal cell carcinoma preferential antigens may change this deficiency soon. In fact, in the near future, monoclonal antibodies will probably reveal many new substances for many urological cancers which can be used for markers serologically, histochemically, and, with their corresponding antibody, for radioimmune imaging and possibly immunotherapy. Now, as then, familiarity with the nuances of the marker and good clinical judgement will be essential.


MATERNAL EFFECTS AND THE PERVASIVE IMPACT OF NESTLING HISTORY ON EGG SIZE IN A PASSERINE BIRD.
Environmental conditions experienced during ontogeny may have important and permanent consequences for life-history traits of individuals. The aim of this work was to determine whether conditions experienced during early life, as expressed by prefledgling condition, have any bearing on the volume of eggs subsequently laid by females in a small passerine bird species, the pied flycatcher (Ficedula hypoleuca). I first show a genetic influence on egg volume by dam-offspring regression. The existence of maternal effects is shown by comparing resemblances between average egg volumes of offspring to those of their paternal and maternal grandmothers. Path analysis shows that when controlling for the influence of maternal egg volume, the average volume of eggs produced in a lifetime is positively related to the body condition of a female measured while she is still at the nest. Thus, body condition at fledgling affects egg volume beyond the ability of maternal egg volume to predict offspring egg volume. Although there may be a persistent maternal effect of egg volume on itself or linked to a property correlated with egg volume, the maternal performance trait involved remains unknown, except for maternal egg volume itself. Given the effects that egg volume may have on reproductive success, which are partly determined prior to leaving the nest, maternal effects may have important consequences for lifetime fitness of offspring.


Remote ischemic preconditioning increases accumulated oxygen deficit in middle-distance runners.
The mediators underlying the putative benefits of remote ischemic preconditioning (IPC) on dynamic whole body exercise performance have not been widely investigated. Our objective was to test the hypothesis that remote IPC improves supramaximal exercise performance in National Collegiate Athletic Association (NCAA) Division I middle-distance runners by increasing accumulated oxygen deficit (AOD), an indicator of glycolytic capacity. A randomized sham-controlled crossover study was employed. Ten NCAA Division I middle-distance athletes [age: 21 ± 1 yr; maximal oxygen uptake (V̇o2max): 65 ± 7 ml·kg-1·min-1] completed three supramaximal running trials (baseline, after mock IPC, and with remote IPC) at 110% V̇o2max to exhaustion. Remote IPC was induced in the right arm with 4 × 5 min cycles of brachial artery ischemia with 5 min of reperfusion. Supramaximal AOD (ml/kg) was calculated as the difference between the theoretical oxygen demand required for the supramaximal running bout (linear regression extrapolated from ~12 × 5 min submaximal running stages) and the actual oxygen demand for these bouts. Remote IPC [122 ± 38 s, 95% confidence interval (CI): 94-150] increased (P < 0.001) time to exhaustion 22% compared with baseline (99 ± 23 s, 95% CI: 82-116, P = 0.014) and sham (101 ± 30 s, 95% CI: 80-123, P = 0.001). In the presence of IPC, AOD was 47 ± 36 ml/kg (95% CI: 20.8-73.9), a 29% increase compared with baseline (36 ± 28 ml/kg, 95% CI: 16.3-56.9, P = 0.008) and sham (38 ± 32 ml/kg, 95% CI: 16.2-63.0, P = 0.024). Remote IPC considerably improved supramaximal exercise performance in NCAA Division I middle-distance athletes. Greater glycolytic capacity, as estimated by increased AOD, is a potential mediator for these performance improvements. NEW & NOTEWORTHY Our novel findings indicate that ischemic preconditioning enhanced glycolytic exercise capacity, enabling National Collegiate Athletic Association (NCAA) middle-distance track athletes to run ~22 s longer before exhaustion compared with baseline and mock ischemic preconditioning. The increase in "all-out" performance appears to be due to increased accumulated oxygen deficit, an index of better supramaximal capacity. Of note, enhanced exercise performance was demonstrated in a specific group of in-competition NCAA elite athletes that has already undergone substantial training of the glycolytic energy systems.


Diagnostic value of cytology of bronchoalveolar fluid for lung diseases of sheep.
Bronchoalveolar lavage fluid was collected postmortem from the lungs of 113 sheep, and total and differential cell counts were analysed in relation to the presence of gross and microscopic lung pathology. The diffuse lung diseases, maedi and adenomatosis, were both characterised by an increase in overall cellularity and by increases in the percentages of lymphocytes and neutrophils, respectively. Focal parasitic lung disease was characterised by an increase in the percentage of eosinophils and mast cells. Consolidated lung lesions were characterised by a slight increase in cellularity but no change in the differential cell profile. In regions of parasitised and consolidated lungs without lesions the differential cell profile was consistent with focal lung pathology, although the slight increase in cellularity observed in the consolidated regions was not observed in the regions without lesions. A decision tree was developed to facilitate the interpretation and indicate the likely predictive capacity of the differential cytology of the fluid.


Acute cerebral ischemia after intracranial bleeding in unilateral moyamoya disease: case report.
A 31-year-old male presenting with intracranial hemorrhage manifesting as deep coma and anisocoria underwent immediate emergency surgery. Three-dimensional computed tomography (CT) angiography revealed stenosis of the right middle cerebral artery (MCA) and perfusion CT immediately after the surgery suggested severe hypoperfusion in the right MCA territory. Postoperative angiography demonstrated right unilateral moyamoya disease. We predicted that brain edema and intracranial pressure (ICP) elevation occurring after the hemorrhage might result in cerebral infarction. Hyperosmotic drugs were contraindicated by dehydration. Therefore, therapeutic hypothermia was induced that controlled the ICP. We considered that the increased ICP, dehydration, vasospasm, and shrinkage of the ruptured vessel comprised the pathogenesis of acute cerebral ischemia after intracranial bleeding. Cerebral hemodynamics should be evaluated during the acute phase of cerebral hemorrhage to prevent subsequent cerebral infarction.


Special cases for proton beam radiotherapy: re-irradiation, lymphoma, and breast cancer.
The dose distributions that can be achieved with protons are usually superior to those of conventional photon external-beam radiation. There are special cases where proton therapy may offer a substantial potential benefit compared to photon treatments where toxicity concerns dominate. Re-irradiation may theoretically be made safer with proton therapy due to lower cumulative lifetime doses to sensitive tissues, such as the spinal cord. Proton therapy has been used in a limited number of patients with rectal, pancreatic, esophageal, and lung cancers. Chordomas and soft tissue sarcomas require particularly high radiation doses, posing additional challenges for re-irradiation. Lymphoma is another special case where proton therapy may be advantageous. Late toxicities from even relatively low radiation doses, including cardiac complications and second cancers, are of concern in lymphoma patients with high cure rates and long life expectancies. Proton therapy has begun to be used for consolidation after chemotherapy in patients with Hodgkin and non-Hodgkin lymphoma. Breast cancer is another emerging area of proton therapy development and use. Proton therapy may offer advantages compared to other techniques in the setting of breast boosts, accelerated partial breast irradiation, and post-mastectomy radiotherapy. In these settings, proton therapy may decrease toxicity associated with breast radiotherapy. As techniques are refined in proton therapy, we may be able to improve the therapeutic ratio by maintaining the benefits of radiotherapy while better minimizing the risks.


Using temporal mining to examine the development of lymphedema in breast cancer survivors.
Secondary lymphedema is a lifetime risk for breast cancer survivors and can severely affect quality of life. Early detection and treatment are crucial for successful lymphedema management. Limb volume measurements can be utilized not only to diagnose lymphedema but also to track progression of limb volume changes before lymphedema, which has the potential to provide insight into the development of this condition. This study aims to identify commonly occurring patterns in limb volume changes in breast cancer survivors before the development of lymphedema and to determine if there were differences in these patterns between certain patient subgroups. Furthermore, pattern differences were studied between patients who developed lymphedema quickly and those whose onset was delayed. A temporal data mining technique was used to identify and compare common patterns in limb volume measurements in patient subgroups of study participants (n = 232). Patterns were filtered initially by support and confidence values, and then t tests were used to determine statistical significance of the remaining patterns. Higher body mass index and the presence of postoperative swelling are supported as risk factors for lymphedema. In addition, a difference in trajectory to the lymphedema state was observed. The results have potential to guide clinical guidelines for assessment of latent and early-onset lymphedema.


Chemical inhibition of potato ABA-8'-hydroxylase activity alters in vitro and in vivo ABA metabolism and endogenous ABA levels but does not affect potato microtuber dormancy duration.
The effects of azole-type P450 inhibitors and two metabolism-resistant abscisic acid (ABA) analogues on in vitro ABA-8'-hydroxylase activity, in planta ABA metabolism, endogenous ABA content, and tuber meristem dormancy duration were examined in potato (Solanum tuberosum L. cv. Russet Burbank). When functionally expressed in yeast, three potato CYP707A genes were demonstrated to encode enzymatically active ABA-8'-hydroxylases with micromolar affinities for (+)-ABA. The in vitro activity of the three enzymes was inhibited by the P450 azole-type inhibitors ancymidol, paclobutrazol, diniconazole, and tetcyclasis, and by the 8'-acetylene- and 8'-methylene-ABA analogues, with diniconazole and tetcyclasis being the most potent inhibitors. The in planta metabolism of [(3)H](±)-ABA to phaseic acid and dihydrophaseic acid in tuber meristems was inhibited by diniconazole, tetcyclasis, and to a lesser extent by 8'-acetylene- and 8'-methylene-ABA. Continuous exposure of in vitro generated microtubers to diniconazole resulted in a 2-fold increase in endogenous ABA content and a decline in dihydrophaseic acid content after 9 weeks of development. Similar treatment with 8'-acetylene-ABA had no effects on the endogenous contents of ABA or phaseic acid but reduced the content of dihydrophaseic acid. Tuber meristem dormancy progression was determined ex vitro in control, diniconazole-, and 8'-acetylene-ABA-treated microtubers following harvest. Continuous exposure to diniconazole during microtuber development had no effects on subsequent sprouting at any time point. Continuous exposure to 8'-acetylene-ABA significantly increased the rate of microtuber sprouting. The results indicate that, although a decrease in ABA content is a hallmark of tuber dormancy progression, the decline in ABA levels is not a prerequisite for dormancy exit and the onset of tuber sprouting.


[Experimental modeling of acute pyelonephritis].
Acute pyelonephritis (AP) predominates among inflammatory infection kidney affections. In accordance to international classifications, AP is an upper urinary tract infection, subdivided into non-complicated (non-obstructive) and complicated (obstructive) forms. The clinical significance of AP presently is defined by the conditions frequent occurrence and its progression into chronic kidney disease. For a limited number of pathogens the involvement in AP is considered proven: representatives of the Enterobacteriaceae family (E.coli, Klebsiella spp., Proteus spp., etc.), Pseudomonas spp., a number of gram-positive microorganisms (S.aureus, Enterococcus spp.). Beside that, over the last 3 decades there have been rare publications in the world literature describing clinical cases of AP caused by microorganisms not readily cultivated on standard mediums (mostly anaerobic). This was accompanied by an idea that AP might develop in case of kidney invasion not only by aerobic, but also by anaerobic microorganisms, which is practically not taken into account in current clinical practice. In this regard it was deemed feasible to perform an analysis of experimental disease models to refine the discussion points of the disease etiology, to do so an attempt of all-encompassing study in the Russian and English literature databases (linical Key, MEDLINE, PubMed, HighWire Press, The Cochrane Library, BioMed Central, Central scientific medical library of the I.M. Sechenov Moscow medical academy, Russian State Library). A total of 356 literature sources have been studied, of which 41 were selected for the current review.


[Incidence of weak sinus syndrome in patients with sinus bradycardia and prognosis].
A total of 270 patients with sinus bradycardia were studied to detect the sick sinus syndrome (SSS) in them and to determine the impact of sex, age, heart rate and atropine test on sinus function recovery time (SFRT) and corrected sinus function recovery time (CSFRT). The study indicated that CSFRT which is pathological at a duration of 525 msec or more was most valuable in the diagnosis of the sick sinus syndrome. Responses to atropine tests were significantly different in healthy persons and in patients with lower automatic sinus function. Increases in heart rate during the atropine test by less than 70% of the baseline suggests an organically decreased automatic function. In patients with sinus bradycardia, the age was related to SFRT to a lesser extent, when the baseline heart rate only in males affected SFRT rather than CSFRT. After atropine administration and its percentage increase, heart rate was found to be closely related to SFRT and CSFRT.


Juvenile fibromyalgia in an adolescent patient with sickle cell disease presenting with chronic pain.
Juvenile fibromyalgia in children with sickle cell disease has not been reported in the literature. We report an adolescent patient with sickle cell whose pain symptoms progressed from having recurrent acute sickle cell pain crisis episodes to a chronic pain syndrome over several years. He was eventually diagnosed with juvenile fibromyalgia based on the clinical history and myofascial tender points and his pain symptoms responded better to multidisciplinary strategies for chronic fibromyalgia pain. Chronic pain in sickle cell disease is an area of poor research, and in addition there is inconsistency in the definition of chronic pain in sickle cell disease. Central sensitisation to pain is shown to occur after recurrent painful stimuli in a genetically vulnerable individual. In a chronic pain condition such as fibromyalgia central sensitisation is thought to play a key role. Fibromyalgia should be considered as one of the main differential diagnosis in any sickle cell patient with chronic pain.


Repeatability of a Dislocation Spinal Cord Injury Model in a Rat-A High-Speed Biomechanical Analysis.
Dislocation is the most common, and severe, spinal cord injury (SCI) mechanism in humans, yet there are few preclinical models. While dislocation in the rat model has been shown to produce unique outcomes, like other closed column models it exhibits higher outcome variability. Refinement of the dislocation model will enhance the testing of neuroprotective strategies, further biomechanical understanding, and guide therapeutic decisions. The overall objective of this study is to improve biomechanical repeatability of a dislocation SCI model in the rat, through the following specific aims: (i) design new injury clamps that pivot and self-align to the vertebrae; (ii) measure intervertebral kinematics during injury using the existing and redesigned clamps; and (iii) compare relative motion at the vertebrae-clamp interface to determine which clamps provide the most rigid connection. Novel clamps that pivot and self-align were developed based on the quantitative rat vertebral anatomy. A dislocation injury was produced in 34 rats at C4/C5 using either the existing or redesigned clamps, and a high-speed X-ray device recorded the kinematics. Relative motion between the caudal clamp and C5 was significantly greater in the existing clamps compared to the redesigned clamps in dorsoventral translation and sagittal rotation. This study demonstrates that relative motions can be of magnitudes that likely affect injury outcomes. We recommend such biomechanical analyses be applied to other SCI models when repeatability is an issue. For this dislocation model, the results show the importance of using clamps that pivot and self-align to the vertebrae.


[Leishmaniasis in dogs in Germany: epidemiological case analysis and alternatives to conventional causal therapy].
Between January 1993 and September 1995 Leishmania infections were detected in 236 dogs in Germany. Of the 132 epidemiologically evaluable dogs, 35 animals had travelled with their owners abroad in endemic areas and 97 dogs had been brought from these regions to Germany by animal lovers. As regards to the possible location of infection it has been registered that these dogs have been taken to countries of the Mediterranean Sea (Spain, France, Italy, Turkey) or to Portugal or had been imported from there. Therapeutic trials with allopurinol revealed that this drug administered at daily doses of 20 mg/kg bodyweight p.o. over weeks disposes of a sufficient therapeutic efficacy against canine leishmaniosis.


OpenNahele: the open Hawaiian forest plot database.
This data paper provides a description of OpenNahele, the open Hawaiian forest plot database. OpenNahele includes 530 forest plots across the Hawaiian archipelago containing 43,590 individuals of 185 native and alien tree, shrub and tree fern species across six islands. We include estimates of maximum plant size (D950.1 and Dmax3) for 58 woody plant species, a key functional trait associated with dispersal distance and competition for light. OpenNahele can serve as a platform to test key ecological, evolutionary and conservation questions in a hotspot archipelago. OpenNahele is the first database that compiles data from a large number of forest plots across the Hawaiian archipelago to allow broad and high resolution studies of biodiversity patterns.Keywords: Hawaii, forests, islands, biodiversity, community ecology, evolutionary ecology.


Recently identified colon cancer predispositions: MYH and MSH6 mutations.
Single-gene germline mutations conferring a high lifetime risk of colorectal cancer (CRC) account for up to 6% of all CRC cases. The most widely studied monogenic colorectal cancer syndromes include familial adenomatous polyposis (FAP) and Lynch syndrome. However, additional syndromes continue to be defined and new predisposition genes are continuing to be identified. Most recently, MYH-associated polyposis (MAP) and an "atypical Lynch syndrome" related to the presence of MSH6 mutations have been linked to an increased risk of CRC. In this review, we summarize basic information related to these newly recognized gene mutations, including the accumulating data on the prevalence and penetrance of deleterious mutations, as well as the management options for identified carriers and their families. Recognizing these heritable syndromes is essential and predictive genetic testing will continue to transform the field of cancer risk assessment by offering the opportunity to focus on more precise risk management and cancer prevention.


Evaluation of Endovenous Laser Ablation in the Management of Varicose Veins.
Background The treatment of varicose veins has undergone tremendous changes over the years. High ligation of the saphenofemoral junction (SFJ) and stripping of the great saphenous vein (GSV) have been considered standard treatments for GSV insufficiency for over a century and are still adopted as the preferred method in the majority of surgical centers in North Africa. However, the increase in minimally invasive treatments such as endovenous thermal ablation (EVTA), radiofrequency ablation (RFA), ultrasound-guided foam sclerotherapy, and cryo-stripping has produced excellent results. Most patients who underwent these minimally invasive treatments were satisfied with their outcomes. Methodology and results In this clinical and prospective study, 30 cases (19 male and 11 female) of primary varicose veins underwent endovenous laser ablation (EVLA), and their outcomes were reviewed, and their results were satisfying to the patients. After EVLA with or without sclerotherapy, no major complications occurred (recurrence or recanalization) at the time of the study, although minor complications were quite common and included bruising or ecchymosis, postoperative pain that required analgesics, superficial thrombophlebitis, and skin burns that were very responsive to medical treatment. Conclusion Endovenous laser ablation continues to be a valid minimally invasive method for treating varicose veins with minimal complications and a very short recovery period, which appeals to patients.


Barium silicate nanoparticles, an efficient catalyst for one-pot green synthesis of α-benzyl amino coumarin derivatives as potential chemotherapeutic agents.
A new, simple, and efficient method for synthesis of α-benzyl amino coumarin and its derivatives (1-24) is described via a one-pot, three-component condensation of aromatic aldehydes, amine, and 4-hydroxycoumarin under green chemistry conditions: water as a solvent and BaSiO3 nanoparticles as catalyst. BaSiO3 nanoparticles and all synthesized derivatives were characterized by multiple methods including; XRD, NMR, and FE-SEM. This method which gives higher yields, is also less expensive, and more environmentally friendly compared with other methods in the literature. In silico physicochemical and pharmacokinetics analyses were done on all synthesized compounds and indicated that these α-benzyl amino coumarins would be effective scaffolds for the future development of chemotherapeutic agents.


[Sildenafil and nitric oxide inhalation in neonatal pulmonary hypertension. Three case reports].
Neonatal persistent pulmonary hypertension (NPPH) is characterised by persistently high pulmonary vascular resistance (PVR). Sildenafil has recently been suggested as an alternative to or an associative therapy with inhaled nitric oxide (iNO) to reduce mortality (10-40%) and morbidity (major neurologic disabilities among surviving newborns remains approximately 15-60%). The objective is to report three cases of NPPH treated with sildenafil in association of iNO. Echocardiography examination of three newborn babies with respiratory distress syndrome and a gestational age between 33 and 39 weeks revealed pulmonary hypertension following early onset sepsis. Synchronized intermittent mandatory ventilation (SIMV) and surfactant therapy had no effect on oxygen saturation (SatO2) and oxygen alveolar-arterial difference (AaDO2). High frequency oscillatory ventilation (HFOV) and iNO therapy proved to be equally ineffective. Oral sildenafil was administered at 2 mg/Kg/6 hs. A gradual but significant improvement in oxygenation was achieved and a reduction in AaDO2 along with oxygenation index (OI) and pulmonary arterial pressure (PAP) was observed in the first 6-10 hrs after administration of sildenafil. The therapy was maintained for 36-48 hrs with total success. A beneficial pulmonary vasodilator effect was obtained in treating NPPH with sildenafil where conventional methods had failed. Sildenafil used in association with iNO reduces the duration of treatment, the quantity of iNO normally required and the associated toxic effects. A multicentric, randomized trial could be useful in demonstrating the safety, efficacy, doses and forms of administration of sildenafil.


Fetoscopic Endoluminal Tracheal Occlusion in Fetuses with Severe Diaphragmatic Hernia: A Three-Year Single-Center Experience.
To report on our experience in the prenatal treatment of severe congenital diaphragmatic hernia (CDH) by fetoscopic endoluminal tracheal occlusion (FETO). Between 2012 and 2014, FETO was performed at our center in 21 cases of CDH considered to be severe based on sonographic measurement of observed/expected lung-to-head ratio (O/E LHR) and side of the defect. We reported pre- and postoperative ultrasound findings, procedure-related complications, pregnancy outcome and survival at 1-3 years of age. The median gestational age (GA) at balloon insertion was 28.1 weeks (range 26.0-31.1) and the median GA at delivery 34.7 weeks (range 31.6-39.0); delivery before 32 and 34 weeks occurred in 2 (9.5%) and 7 (33.3%) cases, respectively. Postnatal survival at 1-3 years of age in the 17 cases with isolated unilateral CDH was 47.1%. The percentage difference between pre-balloon removal O/E LHR and pre-FETO O/E LHR was significantly higher in survivors compared to neonates who died (40.8 vs. 21.2%, respectively; p < 0.05). In this study, FETO was associated with an infant survival of 47% in cases with isolated unilateral severe CDH. The post-FETO increase in O/E LHR was higher in fetuses that survived compared to those who died.


Acute diarrhea in hospitalized children of the municipality of Juiz de Fora, MG, Brazil: prevalence and risk factors associated with disease severity.
Acute diarrhea is a common cause of hospitalization among children under 5 years of age. Knowing the prevalence and risk factors associated with the severity of acute diarrhea is essential to control morbidity and mortality. Describe the prevalence of demographic, epidemiologic and clinical features of children under 6 years of age hospitalized for acute diarrhea, and investigate the association between these determinants and the severity of the diarrheic episode. Retrospective, cross-sectional study, during the period from January, 2005 through December, 2008, in the municipality of Juiz de Fora, MG, Brazil. Files from 6,201 children from 0 to 6 years of age, hospitalized in two public teaching institutions (which account for 84% of all the hospitalizations in the municipality), were assessed. Acute diarrhea was defined as the presence of at least three evacuations of liquid or loose stools, within 24 hours, for a maximum period of 14 days. The patients with acute diarrhea were divided in two groups, according to disease severity, severe diarrhea being considered whenever hospitalization lasted for at least 4 days. Epidemiologic and clinical data were assessed and compared through the application of the chi-squared test and the binomial logistic regression model. The prevalence rate for admission due to acute diarrhea was 8.4%. The factors significantly associated with the severity of the diarrheic episode were: age under 6 months (P = 0.01, OR = 2.762); disease onset during fall (P = 0.033, OR = 1.742), presence of fever (P = 0.017, OR = 1.715) and antibiotic use during hospitalization (P = 0.000, OR = 3.872). Diarrhea is the third most common cause of hospitalization among children under 6 years of age in Juiz de Fora. Young age (under or equal to 6 months), fever, antibiotic use during hospitalization and disease onset during fall are risk factors associated with longer hospital stay.


[The history of tracheotomy].
Tracheotomy is one of the oldest operations in medicine. The development of tracheotomy from antiquity to our time is reported. After the beginnings of the operation in Greek and Roman medicine, the operation was called laryngotomy or bronchotomy. It was Heister who coined the name "tracheotomy". Tracheotomy is still an important operation even after more than 2000 years. In recent years there has been a change from simple tracheotomy to plastic tracheostomy.


[The Sigmund Freud - Romain Rolland letters (1923-1936)].
This correspondence evolves on three planes: that of a dialogue between an atheistic Jew and a solitary Christian interested in mysticism, that is also a dialogue between a Frenchman attracted by German culture and an inhabitant of Vienna who was particularly attached to France, as well as being an exchange of ideas on the origins of literary and scientific creation. The central debate on the question of the oceanic heeling suggested by Romain Rolland led Sigmund Freud to take up again an essential point in his self-analysis that had remained unanalysed at the time of his exchange with Fliess: his relationship with an original mother image.


Prognostic influence of office and ambulatory blood pressures in resistant hypertension.
The prognostic value of office and ambulatory blood pressures (BPs) in patients with resistant hypertension is uncertain. This prospective study investigates the importance of office and ambulatory BPs as predictors of cardiovascular morbidity and mortality. At baseline, 556 resistant hypertensive patients underwent clinical-laboratory and 24-hour ambulatory BP monitoring examinations. Primary end points were a composite of fatal and nonfatal cardiovascular events and all-cause and cardiovascular mortalities. Multiple Cox regression was used to assess associations between BP and subsequent end points. After median follow-up of 4.8 years, 109 patients (19.6%) reached the primary end point, and 70 all-cause deaths (12.6%) occurred (46 had cardiovascular causes). After adjustment for age, sex, body mass index, diabetes mellitus, smoking, physical inactivity, dyslipidemia, previous cardiovascular diseases, serum creatinine level, and number of antihypertensive drugs in use, no office BP showed any prognostic value. After further adjustment for office BP, higher mean ambulatory BPs were independent predictors of the composite end point. The hazard ratios associated with a 1-SD increment in daytime and nighttime systolic BP were 1.26 (95% confidence interval, 1.04-1.53) and 1.38 (1.13-1.68), respectively; the corresponding values for diastolic BP were 1.31 (1.05-1.63) and 1.36 (1.10-1.69). Ambulatory systolic and diastolic BP were equivalent predictors, and both were better than pulse pressure; nighttime BP was superior to daytime BP. For all-cause mortality, only the ambulatory BP monitoring diagnosis of true resistant hypertension was an independent predictor. Higher ambulatory BP predicts cardiovascular morbidity and mortality in resistant hypertensive patients, whereas office BP has no prognostic value.


[An integrative model of the psychological benefits of gardening in older adults].
This review of the literature tackles the question of the psychological benefits linked to gardening in older adults. First, the current data on these benefits are reviewed, and the findings reveal that gardening is linked to feelings of accomplishment, well-being and peace, a decrease of depressive symptoms, a protective effect on cognitive functions as well as to the development of social links for community living older adults. In institutionalized older adults, gardening promotes internal locus of control and well-being, and is related to a decrease of sadness and anxiety. Second, several explanatory theories are discussed. All of them postulate an action on the cognitive and/or emotional spheres, which were included into a integrated model that must be tested in future research. In conclusion, gardening appears to be a beneficial activity for promoting older adults' functioning but the current knowledge still has to be extended to understand the specific mechanisms of action. This deeper understanding is necessary in order to improve the future actions depending on this activity.


Structures, electron affinities, and harmonic vibrational frequencies of the simplest alkyl peroxyl radicals and their anions.
The molecular structures and electron affinities of the R-OO/R-OO(-) (R = CH3, C2H5, n-C3H7, n-C4H9, n-C5H11, i-C3H7, t-C4H9) species have been determined using seven different density functional or hybrid Hartree-Fock density functional methods. The basis set used in this work is of double-zeta plus polarization quality with additional diffuse s-type and p-type functions, denoted DZP++. The geometries are fully optimized with each density functional theory method. Harmonic vibrational frequencies were found to be within 3.1% of available experimental values for most functionals. Two different types of the neutral-anion energy separations reported in this work are the adiabatic electron affinity and the vertical detachment energy. The most reliable adiabatic electron affinities obtained at the DZP++ BP86 level of theory are 1.150 (CH3OO), 1.124 (C2H5OO), 1.146 (n-C3H7OO), 1.173 (n-C4H9OO), 1.184 (n-C5H11OO), 1.145 (i-C3H7OO), and 1.114 eV (t-C4H9OO). Compared with the experimental values, the average absolute error of the BPW91 method is 0.05 eV.


Production and characterization of recombinant human Ku antigen.
Ku is an ubiquitous nuclear heterodimeric protein consisting of p70 and p86 subunits that binds double-stranded DNA termini and associates with chromosomes in vivo. It was originally described as an autoantigen in patients with certain autoimmune diseases. The individual subunits of Ku have been difficult to isolate from human cells without denaturation and attempts to produce functional recombinant Ku have been largely unsuccessful. Here, we utilize two recombinant baculoviral vectors that carry p70 or p86 cDNA and express the Ku subunits individually as well as assemble them into the complete Ku heterodimer. In an electrophoretic mobility shift assay, recombinant Ku binds to linear double-stranded DNA but not to supercoiled, nicked circular, nor linear single-stranded DNA. Neither subunit binds DNA by itself indicating that heterodimerization is essential for function. We also describe a simple purification method for the isolation of highly purified recombinant Ku using a hexahistidine tag. The baculovirus expression system provides a stable and efficient source of not only the p70 and p86 subunits but also the functional Ku heterodimer.


What do nurses know?
This paper defends an epistemic conservatism - propositional knowing-that suffices for capturing all the fine details of the knowledge of experienced nurses that depends on the complex ways in which they are embedded in shared fields of activity. I argue against the proliferation of different ways of knowing associated with the work of Dreyfus and Benner. I show how propositional knowledge can capture the detail of the phenomenology that motivates the Dreyfus/Benner proliferation.


Immunohistochemical localization of microsomal PGE synthase-1 and cyclooxygenases in male mouse reproductive organs.
We investigated the tissue distribution and cellular localization of microsomal PGE synthase-1 (mPGES-1) and cyclooxygenase (COX)-1 and -2 in the male mouse reproductive organs. Northern blotting revealed that the mPGES-1 mRNA was expressed intensely in the epididymis and weakly in the lung, spleen, skin, kidney, colon, and brain. In the male reproductive tract, the expression of mPGES-1 increased from the testis to the cauda epididymis and was highest in the vas deferens when examined by Northern blotting, RT-PCR, and Western blotting. By immunohistochemistry, mPGES-1 was detected in Leydig cells of the testis and in epithelial cells of the epididymis, vas deferens, and seminal vesicles. In addition, the caput and cauda regions of the epididymis and the vas deferens in this order showed a progressive increase in the expression of COX-1 mRNA and immunoreactivity, whereas COX-2 was dominantly expressed in the vas deferens. COX-1 was localized in epithelial cells of the caput, corpus and cauda epididymis and of the vas deferens, and COX-2 was evident in epithelial cells of the distal cauda epididymis and vas deferens. These results show that mPGES-1 is expressed coordinately with COX-1 and COX-2 and is involved in PGE(2) production in male genital organs.


The insulinotrophic effect of insulin-like peptide 5 in vitro and in vivo.
Insulin-like peptide 5 (INSL5), a member of the insulin/relaxin superfamily, can activate the G-protein-coupled receptor relaxin/insulin-like family peptide receptor 4 (RXFP4), but its precise biological functions are largely unknown. Recent studies suggest that INSL5/RXFP4 is involved in the control of food intake and glucose homoeostasis. We report in the present study that RXFP4 is present in the mouse insulinoma cell line MIN6 and INSL5 augments glucose-stimulated insulin secretion (GSIS) both in vitro and in vivo. RXFP4 is also expressed in the mouse intestinal L-cell line GLUTag and INSL5 is capable of potentiating glucose-dependent glucagon-like peptide-1 (GLP-1) secretion in GLUTag cells. We propose that the insulinotrophic effect of INSL5 is probably mediated through stimulation of insulin/GLP-1 secretion and the INSL5/RXFP4 system may be a potential therapeutic target for Type 2 diabetes.


Secretory immunoglobulin A obtained from pooled human colostrum and milk for oral passive immunization.
Passive immunization is useful in cases of immunodeficiencies or infectious diseases, but usually seric gammaglobulin or hyperimmune sera are administered parenterally, providing good systemic immunization, though with low protection of the mucosal surfaces. The oral administration of secretory antibodies, especially surface immunoglobulin (SIg)A, which is perfectly adapted to the mucosal environment, would therefore, be preferable. The aim of the present study was to obtain a SIgA preparation from pooled human colostrum and milk, which should maintain the essential properties of the antibodies suitable for clinical oral administration. IgA preparations were obtained from colostrum and milk pools by salt precipitation. The final products were evaluated in terms of yield and purity, as well as antibody activity to bacterial antigens and toxins and inhibitory activity of bacterial adhesion to epithelial cells. The best yield and purity were achieved when the colostrum pool was used as a source of IgA; the final product showed very few bands of protein contamination. The IgA preparations preserved the antibody reactivity against various microbial antigens, well comparable with the reactivity exhibited by the original milk and colostrum pools. SIgA preparations were able to inhibit greatly the adhesion of enteropathogenic Escherichia coli to Hep-2 cells and the invasion of enteroinvasive E. coli. These promising results show the feasibility of obtaining SIgA suitable for oral use, which may in future be administered to immunodeficient patients with gastrointestinal manifestations, from human colostrum and milk.


Spiritual issues of people living and dying with advanced heart failure in Kenya: a qualitative serial interview study.
Exploring patients' spiritual issues is vital for informing holistic care. The spiritual concerns of patients living and dying with advanced heart failure in sub-Saharan Africa remains unknown. Our aim was to describe spiritual issues in the context of the lived experiences of patients with heart failure in Kenya. We purposively recruited 18 patients admitted with advanced heart failure at a rural district hospital in Kenya. We conducted serial in-depth interviews with patients at 0, 3 and 6 months after recruitment. We conducted bereavement interviews with their carers. Interviews were recorded, transcribed into English and analysed using a thematic approach, assisted by Nvivo software package. Patients expressed traditional and Christian spiritual beliefs in response to their illness. At diagnosis, some patients felt their illness had occurred because they had wronged God, while others felt betrayed by God. Some expressed comfort from God and optimism believing that God was in control and would heal their illness. During acute episodes patients questioned whether witchcraft or curses caused their illness. Younger patients experienced more spiritual distress. Although church fellowship generally offered spiritual and social support, some patients felt let down by the church which they perceived to favour those who offered more tithes. This is the first study to explore the spiritual issues of people living with advanced heart failure in Kenya. Understanding patients' spiritual concerns is important for developing evidence-based patient-centred holistic care to promote multidimensional well-being.


Anti-gamma interferon and anti-interleukin-6 antibodies affect staphylococcal enterotoxin B-induced weight loss, hypoglycemia, and cytokine release in D-galactosamine-sensitized and unsensitized mice.
Administration of staphylococcal enterotoxin B (SEB) to BALB/c mice was found to induce a cytokine release syndrome hallmarked by weight loss and hypoglycemia. A neutralizing monoclonal antibody against gamma interferon (IFN-gamma) given before SEB counteracted weight loss and prevented hypoglycemia. This protective effect of anti-IFN-gamma antibody was associated with decreased IFN-gamma levels in serum; tumor necrosis factor (TNF) and interleukin-6 (IL-6) levels remained unchanged. A monoclonal anti-IL-6 antibody, known for its ability to cause accumulation of biologically active IL-6 in the circulation, did not modify SEB-induced body weight loss or hypoglycemia. Levels of TNF, IFN-gamma, and IL-6 in serum were all more elevated in anti-IL-6-treated mice than in corresponding SEB-challenged control mice. In D-galactosamine-sensitized mice, SEB-induced weight loss but not hypoglycemia was more severe, resulting mostly in death within 24 h. Higher levels of biologically active TNF and IFN-gamma in serum were noted in these mice than in mice receiving SEB only. In D-galactosamine-sensitized mice, anti-IFN-gamma antibody did prevent hypoglycemia but failed to reduce the severity of the syndrome. Again, TNF levels in anti-IFN-gamma-treated mice remained unchanged. Pretreatment with anti-IL-6 antibody temporarily attenuated SEB-induced hypoglycemia in sensitized mice. Thus, at 6 h post-SEB injection, anti-IL-6-treated mice were less hypoglycemic than corresponding controls. However, at 24 h, hypoglycemia was significantly aggravated. Concomitantly, IL-6 levels were dramatically increased. Neither anti-IFN-gamma nor anti-IL-6 antibody treatment modulated mortality levels in D-galactosamine-sensitized mice. The data obtained with anti-IFN-gamma antibody clearly indicate that endogenous IFN-gamma is instrumental in bringing about hypoglycemia and body weight loss in mice exposed to SEB but also that hypoglycemia is not a crucial determinant of mortality in D-galactosamine-sensitized mice. The data obtained with anti-IL-6 antibody indicate that endogenous IL-6 is involved in regulating the levels of TNF and IFN-gamma in serum.


Metal seed layer thickness-induced transition from vertical to horizontal growth of MoS2 and WS2.
Two-dimensional (2D), layered transition metal dichalcogenides (TMDCs) can grow in two different growth directions, that is, horizontal and vertical. In the horizontal growth, 2D TMDC layers grow in planar direction with their basal planes parallel to growth substrates. In the vertical growth, 2D TMDC layers grow standing upright on growth substrates exposing their edge sites rather than their basal planes. The two distinct morphologies present unique materials properties suitable for specific applications, such as horizontal TMDCs for optoelectronics and vertical TMDCs for electrochemical reactions. Precise control of the growth orientation is essential for realizing the true potential of these 2D materials for large-scale, practical applications. In this Letter, we investigate the transition of vertical-to-horizontal growth directions in 2D molybdenum (or tungsten) disulfide and study the underlying growth mechanisms and parameters that dictate such transition. We reveal that the thickness of metal seed layers plays a critical role in determining their growth directions. With thick (>∼ 3 nm) seed layers, the vertical growth is dominant, while the horizontal growth occurs with thinner seed layers. This finding enables the synthesis of novel 2D TMDC heterostructures with anisotropic layer orientations and transport properties. The present study paves a way for developing a new class of 2D TMDCs with unconventional materials properties.


Repair of postauricular defects using a new technique: the swallowtail flap.
We describe a case of an 81-year-old patient, where we used a new technique for the reconstruction of postauricular defects (of 3 x 4 cm diameter). The swallowtail flap is an advancement flap that allows getting beyond the repair of the defect, providing an excellent aesthetic result because the scar is masked in the neck and retroauricular folds and does not alter the shape and projection of the ear.


Inpatient Continuous Glucose Monitoring and Glycemic Outcomes.
Continuous glucose monitoring (CGM) is commonly used in the outpatient setting to improve diabetes management. CGM can provide real-time glucose trends, detecting hyperglycemia and hypoglycemia before the onset of clinical symptoms. In 2011, at the time the Endocrine Society CGM guidelines were published, the society did not recommend inpatient CGM as its efficacy and safety were unknown. While many studies have subsequently evaluated inpatient CGM accuracy and reliability, glycemic outcome studies have not been widely published. In the non-ICU setting, investigational CGM studies have commonly blinded providers and patients to glucose data. Retrospective review of the glucose data reflects increased hypoglycemia detection with CGM. In the ICU setting, data are inconsistent whether CGM can improve glycemic outcomes. Studies have not focused on hospitalized patients with type 1 diabetes mellitus, the population most likely to benefit from inpatient CGM. This article reviews inpatient CGM glycemic outcomes in the non-ICU and ICU setting.


A Diheteroatom Fluoroalkylation Reagent for Preparation of S- and N-Containing Fluoroalkyl Compounds and Sulfonic Acid Polymer.
The first stable diheteroatom fluoroalkylation reagent, 2-((2-azido-1-chloro-1,2,2-trifluoroethyl)thio)pyrimidine (ACTP), has been prepared by a novel method. By using this reagent, various fluorinated thioethers and sulfones have been successfully prepared. The dearylation and dearylation-oxidation of fluoroalkyl 2-pyrimidyl sulfone in one-pot reaction were investigated systematically, and the results demonstrated that both fluoroalkyl sulfinates and sulfonates could be obtained in high yields. In addition, ACTP proved to be useful for the preparation of a fluorinated sulfonic acid proton-exchange membrane.