Follow-up of patients undergoing oncoplastic surgery - more palpable masses and benign biopsies.
Oncoplastic reconstruction is increasingly used in the management of women undergoing breast conserving surgery. We examined the findings on breast exam and imaging of patients who underwent breast conservation with or without oncoplastic reconstruction. We hypothesized that patients undergoing immediate breast reconstruction would present with more palpable and imaging abnormalities compared to lumpectomy alone and undergo therefore more biopsies. All patients undergoing breast conservation with oncoplastic reconstruction for breast cancer between 2009 and 2014 were included in the study group. The control group was created by matching 4 women that underwent lumpectomy alone during the same week to each patient in the study group. The two groups were compared regarding demographics, tumor characteristics, post-operative complaints, breast exam, imaging and biopsies done during follow-up. The study group included 67 women who had lumpectomy and immediate oncoplastic reconstruction and 268 women that underwent lumpectomy alone.Patients undergoing immediate oncoplastic reconstruction had more advanced disease; larger mean tumor size (3.1 cm versus 1.9 cm, P < 0.001), higher rate of involved lymph nodes (48% versus 26%; P < 0.001) and use of neoadjuvant treatment (39% versus 15%; P < 0.001).After oncoplastic reconstruction, new lumps (18% versus 5%; P = 0.004) were found more frequently, and there was a higher rate of women undergoing biopsies (31% versus 11%; P < 0.001). This finding remained significant after controlling for age, type of tumor, use of neoadjuvant treatment and volume of tissue removed. Over ninety percent of biopsies in the oncoplastic group were benign, most commonly-fat necrosis (N = 15, 60% of the biopsies). Immediate oncoplastic reconstruction is associated with increased palpable masses and imaging abnormalities, requiring biopsies. Patients and clinicians should be aware of the benign nature of most of these findings.


High glucose induces podocyte apoptosis by stimulating TRPC6 via elevation of reactive oxygen species.
Podocyte number is significantly reduced in diabetic patients and animal models, but the mechanism remains unclear. In the present study, we found that high glucose induced apoptosis in control podocytes which express transient receptor potential canonical 6 (TRPC6) channels, but not in TRPC6 knockdown podocytes in which TRPC6 was knocked down by TRPC6 silencing short hairpin RNA (shRNA). This effect was reproduced by treatment of podocytes with the reactive oxygen species (ROS), hydrogen peroxide (H2O2). Single-channel data from cell-attached, patch-clamp experiments showed that both high glucose and H2O2 activated the TRPC6 channel in control podocytes, but not in TRPC6 knockdown podocytes. Confocal microscopy showed that high glucose elevated ROS in podocytes and that H2O2 reduced the membrane potential of podocytes and elevated intracellular Ca(2+) via activation of TRPC6. Since intracellular Ca(2+) overload induces apoptosis, H2O2-induced apoptosis may result from TRPC6-mediated elevation of intracellular Ca(2+). These data together suggest that high glucose induces apoptosis in podocytes by stimulating TRPC6 via elevation of ROS.


Characterization and evaluation of a modified local lymph node assay using ATP content as a non-radio isotopic endpoint.
The murine local lymph node assay (LLNA) is an accepted and widely used method for assessing the skin-sensitizing potential of chemicals. Here, we describe a non-radio isotopic modified LLNA in which adenosine triphosphate (ATP) content is used as an endpoint instead of radioisotope (RI); the method is termed LLNA modified by Daicel based on ATP content (LLNA-DA). Groups of female CBA/JNCrlj mice were treated topically on the dorsum of both ears with test chemicals or a vehicle control on days 1, 2, and 3; an additional fourth application was conducted on day 7. Pretreatment with 1% sodium lauryl sulfate solution was performed 1 h before each application. On day 8, the amount of ATP in the draining auricular lymph nodes was measured as an alternative endpoint by the luciferin-luciferase assay in terms of bioluminescence (relative light units, RLU). A stimulation index (SI) relative to the concurrent vehicle control was derived based on the RLU value, and an SI of 3 was set as the cut-off value. Using the LLNA-DA method, 31 chemicals were tested and the results were compared with those of other test methods. The accuracy of LLNA-DA vs LLNA, guinea pig tests, and human tests was 93% (28/30), 80% (20/25), and 79% (15/19), respectively. The estimated concentration (EC) 3 value was calculated and compared with that of the original LLNA. It was found that the EC3 values obtained by LLNA-DA were almost equal to those obtained by the original LLNA. The SI value based on ATP content is similar to that of the original LLNA as a result of the modifications in the chemical treatment procedure, which contribute to improving the SI value. It is concluded that LLNA-DA is a promising non-RI alternative method for evaluating the skin-sensitizing potential of chemicals.


Atypical stoichiometry for a 3D bimetallic oxalate-based long-range ordered magnet exhibiting high proton conductivity.
The reproducible formation of a 3D oxalate based coordination compound of formula (NH4)5[Mn(II)2Cr(III)3(ox)9]·10H2O, with an unusual Mn(II)/Cr(III) ratio, is presented. The original topology of the anionic network leads to antiferromagnetic long-range ordering whereas its guests favour high humidity-dependent proton conductivity.


Impacts of rhizoremediation and biostimulation on soil microbial community, for enhanced degradation of petroleum hydrocarbons in crude oil-contaminated agricultural soils.
Hydrocarbonoclastic bacterial strains were isolated from rhizosphere of plants growing in crude oil-contaminated sites of Assam, India. These bacteria showed plant growth-promoting attributes, even when exposed to crude oil. Two independent pot trials were conducted to test the rhizodegradation ability of the bacterial consortium in combination of plants Azadirchta indica or Delonix regia in crude oil-contaminated soil. Field experiments were conducted at two crude oil-contaminated agricultural field at Assam (India), where plants (A. indica or D. regia) were grown with the selected bacterial consortium consisting of five hydrocarbonoclastic bacterial isolates (Gordonia amicalis BB-DAC, Pseudomonas aeruginosa BB-BE3, P. citronellolis BB-NA1, Rhodococcus ruber BB-VND, and Ochrobactrum anthropi BB-NM2), and NPK was added to the soil for biostimulation. The bacterial consortium-NPK biostimulation led to change in rhizosphere microbiome with enhanced degradation of petroleum hydrocarbons (PHs) in soils contaminated with crude oil. After 120 days of planting A. indica + consortium + NPK treatment, degradation of PHs was found to be up to 67%, which was 55% with D. regia with the same treatment. Significant changes in the activities of plant and soil enzymes were also noted. The shift is bacterial community was also apparent as with A. indica, the relative abundance of Proteobacteria, Actinobacteria, and Acidobacteria increased by 35.35%, 26.59%, and 20.98%, respectively. In the case of D. regia, the relative abundance of Proteobacteria, Actinobacteria, and Acidobacteria were increased by 39.28%, 35.79%, and 9.60%, respectively. The predicted gene functions shifted in favor of the breakdown of xenobiotic compounds. This study suggests that a combination of plant-bacterial consortium and NPK biostimulation could be a productive approach to bioengineering the rhizosphere microbiome for the purpose of commercial bioremediation of crude oil-contaminated sites, which is a major environmental issue faced globally.


Interferon-alpha-2b plus ribavirin: a review of its use in the management of chronic hepatitis C.
Relatively few patients (< or =20%) with chronic hepatitis C achieve a sustained virological response after interferon-alpha monotherapy. Hence, alternative treatment strategies such as the addition of the broad spectrum antiviral agent ribavirin to interferon-alpha-2b have been investigated. Combination therapy with subcutaneous interferon-alpha-2b [3 million units (MU) three times per week] plus oral ribavirin (1000 to 1200 mg/day) has proven effective in several well designed trials of 24 to 48 weeks' duration in adult patients with compensated chronic hepatitis C. Compared with interferon-alpha-2b (3 or 6 MU three times per week) with or without placebo, combination treatment with interferon-alpha-2b plus ribavirin significantly enhanced end-of-treatment and sustained virological and biochemical response rates in treatment-naive and treatment-experienced patients [sustained virological response rates in treatment-naive recipients (6 to 19% vs 31 to 43% of patients); sustained overall (virological plus biochemical) response rates in nonresponders to (1 vs 14%) or relapsers (4 to 5% vs 30 to 44%) after previous interferon-alpha monotherapy]. Forty-eight weeks of combination therapy was superior to 24 weeks in treatment-naive patients infected with hepatitis virus C (HCV) genotype 1, whereas response rates were similar at 24 and 48 weeks in those infected with other HCV genotypes. Furthermore, there were marked improvements in histological inflammatory scores in patients who responded to treatment with either interferon-alpha-2b plus ribavirin or interferon-alpha-2b alone. Although adverse events associated with either drug during combination therapy occurred frequently, these were generally mild to moderate in intensity and were consistent with those reported for each individual agent. Twenty-six percent of patients required dosage modifications of one or both drugs during combination therapy. Interferon-alpha-2b plus ribavirin is an efficacious first- and second-line therapy in adult patients with compensated chronic hepatitis C, significantly improving sustained virological and biochemical responses versus interferon-alpha-2b monotherapy. The tolerability profile of interferon-alpha-2b plus ribavirin therapy is consistent with the individual profiles of these agents with no evidence of additive effects. The place of interferon-alpha-2b plus ribavirin combination therapy in relation to newer agents, including pegylated interferons-alpha and other multidrug regimens, remains to be determined in this rapidly evolving area of therapeutic management. Currently, combination therapy with interferon-alpha-2b plus ribavirin is recommended as first-line therapy for patients with chronic hepatitis C and compensated liver disease, and is an option for use as second-line therapy in those who have relapsed after, or failed to respond to, previous treatment with interferon-alpha.


Host factors and environmental determinants associated with skin test reactivity and eosinophilia in a community-based population study.
We examined the relationship of host factors (age, gender) and environmental determinants (smoking status, area of residence) to indicators of allergy (skin test reactivity and eosinophil count) in a random population sample in the Netherlands. Positive skin test reactivity was associated with age (decreasing with increasing age), with male gender (versus female gender), and with urban residence (versus rural residence). Positive skin test reactivity was not associated with smoking. Elevated eosinophil counts were associated with male gender (versus female gender), with urban residence (versus rural residence), and with current smoking (versus never smoking). Elevated eosinophil counts were not clearly associated with age (if adjusted for the age-related effects of skin test reactivity). Additionally, this study specifically demonstrates that skin test reactivity increases with increasing eosinophil count and vice versa, indicating that the two traits are interrelated. Furthermore, this interrelationship was demonstrated to be age-dependent (decreasing with increasing age).


Role of the liver in the rat intestinal s-IgA system.
Rat bile is an important source of s-IgA and FSC about 10 mg of s-IgA are poured daily in the duodenum via the bile. The normal rat liver is capable of actively transferring IgA from the circulation into bile against a strong concentration gradient. Circulating IgA transferred in bile was bound to SC. Ligature of the rat bile duct induces a large and selective increase of the IgA level in serum. All this additional IgA is s-IgA and even FSC appears in serum after bile duct obstruction. The liver appears to have an important reinforcing role in the intestinal s-IgA system of the rat.


High-density genetic linkage map construction and cane cold hardiness QTL mapping for Vitis based on restriction site-associated DNA sequencing.
Cold hardiness is an important agronomic trait and can significantly affect grape production and quality. Until now, there are no reports focusing on cold hardiness quantitative trait loci (QTL) mapping. In this study, grapevine interspecific hybridisation was carried out with the maternal parent 'Cabernet sauvignon' and paternal parent 'Zuoyouhong'. A total of 181 hybrid offspring and their parents were used as samples for restriction-site associated DNA sequencing (RAD). Grapevine cane phloem and xylem cold hardiness of the experimental material was detected using the low-temperature exotherm method in 2016, 2017 and 2018. QTL mapping was then conducted based on the integrated map. We constructed a high-density genetic linkage map with 16,076, 11,643, and 25,917 single-nucleotide polymorphism (SNP) markers anchored in the maternal, paternal, and integrated maps, respectively. The average genetic distances of adjacent markers in the maps were 0.65 cM, 0.77 cM, and 0.41 cM, respectively. Colinearity analysis was conducted by comparison with the grape reference genome and showed good performance. Six QTLs were identified based on the phenotypic data of 3 years and they were mapped on linkage group (LG) 2, LG3, and LG15. Based on QTL results, candidate genes which may be involved in grapevine cold hardiness were selected. High-density linkage maps can facilitate grapevine fine QTL mapping, genome comparison, and sequence assembly. The cold hardiness QTL mapping and candidate gene discovery performed in this study provide an important reference for molecular-assisted selection in grapevine cold hardiness breeding.


Amino Acids Rather than Glucose Account for the Majority of Cell Mass in Proliferating Mammalian Cells.
Cells must duplicate their mass in order to proliferate. Glucose and glutamine are the major nutrients consumed by proliferating mammalian cells, but the extent to which these and other nutrients contribute to cell mass is unknown. We quantified the fraction of cell mass derived from different nutrients and found that the majority of carbon mass in cells is derived from other amino acids, which are consumed at much lower rates than glucose and glutamine. While glucose carbon has diverse fates, glutamine contributes most to protein, suggesting that glutamine's ability to replenish tricarboxylic acid cycle intermediates (anaplerosis) is primarily used for amino acid biosynthesis. These findings demonstrate that rates of nutrient consumption are indirectly associated with mass accumulation and suggest that high rates of glucose and glutamine consumption support rapid cell proliferation beyond providing carbon for biosynthesis.


Mutagenicity of 4,4'-methylene-bis-(2-chloroaniline) "MOCA" and its N-acetyl derivatives in S. typhimurium.
4,4'-methylene-bis-(2-chloroaniline) ("MOCA") and two identified urinary N-acetyl and N,N'-diacetyl derivatives were tested in a Salmonella/mammalian microsome assay. No mutagenic activity was observed without rat liver S9 mix activation. In the presence of rat liver S9 mix, the chemicals were mutagens, but the mutagenicity of N-acetyl derivatives to strain TA100 was reduced when compared to that of "MOCA", and a greater amount of S9 was required to exhibit the mutagenicity of the N,N'-diacetyl-"MOCA". These data suggest that N-acetylation does not account for the mutagenic effectiveness of "MOCA".


Distribution of two forms of somatostatin and peptides belonging to the pancreatic polypeptide family in tissues of larval lampreys, Petromyzon marinus L.: an immunohistochemical study.
Immunohistochemistry on tissues of larval lampreys, Petromyzon marinus L., was used to determine the distribution of invariant somatostatin-14 (SST-14) and lamprey somatostatin-34 (SST-34) in the brain while antisera against porcine peptide tyrosine tyrosine (PYY), human neuropeptide Y (NPY), anglerfish peptide YG (aPY), salmon glucagon-like peptide (GLP), SST-14, and SST-34 were used in studies of the pancreas and anterior intestine. In the brain, SST-14 is the major form of somatostatin. SST-14- and SST-34-immunoreactive nerve fibers are distributed throughout the telencephalon, diencephalon, and mesencephalon. In the latter region SST-14 immunoreactivity is concentrated in nerve tracts in the nucleus interpeduncularis. Nerve cells within the olfactory bulbs are immunoreactive only to anti-SST-34. Cells immunostained with anti-SST-14 were localized within the ependymal and subependymal layers of the pars ventralis hypothalami and the subependymal layers of the pars dorsalis thalami. SST-14-immunoreactive perikarya are also distributed within the tegmentum mesencephali. Nerve fibers and cells immunoreactive to anti-SST-34 are detected in the pars ventralis hypothalami but these cells do not colocalize SST-14. Pancreatic islets, distributed within the epithelium and in the submucosal connective tissue at the esophageal-intestinal junction, are only immunoreactive to anti-insulin. The antisera revealed three distinct cell types in the intestinal epithelium: type 1 colocalizes aPY, NPY, and PYY; type 2 colocalizes SST-14 and SST-34; and type 3 demonstrates immunoreactivity only to anti-SST-34. Immunoreactivity to anti-GLP is absent.


High molecular weight DNA intermediates synthesized by permeabilized L cells.
Mouse L cells rendered permeable to deoxynucleoside triphosphates synthesize DNA as an extension of replication forks that were active in the intact cells. The permeabilization process does not affect the size of the bulk cell DNA. Intermediate molecular weight DNA, synthesized in the intact cells, is neither degraded to small molecular weight DNA nor processed into bulk cell DNA following the permeabilization process. DNA synthesized by the permeable cells demonstrates a heterogenous distribution in alkaline sucrose gradients, with peaks at 26 S and 71 S. Pulse-chase experiments demonstrate that these two classes of DNA intermediates do not have a precursor product relation. They appear to be synthesized independently and at the same rate. The results are compatible with continuous synthesis of DNA along one template strand and discontinuous synthesis along the opposite strand. DNA synthesis in isolated L cell nuclei was compared to the process in permeabilized cells with the results demonstrating that the rate of DNA synthesis is slower in the nuclei than it is in the permeable cells. Alkaline sucrose gradient studies demonstrate that the DNA synthesized by isolated nuclei is smaller than the DNA synthesized by the permeable cells.


A comparative study of the dose-dependent effects of low level and high intensity photobiomodulation (laser) therapy on pain and electrophysiological parameters in patients with carpal tunnel syndrome.
Carpal tunnel syndrome (CTS) is a common peripheral nerve disorder of the wrist. Nonsurgical treatments e.g. laser therapy may cause potential beneficial effects. To compare the dose dependent effects of low level laser therapy (LLLT) and high intensity laser therapy (HILT) on pain and electrophysiology studies in patients with CTS. Double-blind randomized controlled trial. Outpatient physiotherapy clinic. Ninety-eight participants with CTS, aged between 20 to 60 years, were randomly assigned to five groups. All participants undertook four standard exercises, with one group serving as exercise-only controls. Patients were randomly allocated to either high or low fluence LLLT or high or low fluence HILT received over 5 sessions. All patients were assessed by visual analogue scale, median compound muscle action potential (CMAP) and sensory nerve conduction studies before and 3 weeks after the interventions. VAS was significantly lower in all groups after 3 weeks (P<0.05). CMAP latency decreased in all groups. The interaction of group and time (5×2) was significant for pain (P<0.001), the latency of CMAP (P=0.001) and CMAP amplitude (P=0.02). The interaction of group and time was not significant for the CMAP conduction velocity, sensory nerve latency and amplitude (P>0.05). HILT with a power of 1.6 W and low fluence of 8 J/cm2 was superior in reduction of pain and improvement of the median motor nerve electrophysiological studies compared to LLLT and exercise-only control groups. LLLT and HILT in conjunction with exercise program are effective in reducing pain and improving median motor nerve conduction studies of the patients with CTS. It seems that high power and low fluence laser therapy is better than LLLT and exercise interventions to treat these patients.


Getting More from the Sleep Recording.
Sleep studies have typically followed criteria established many decades ago, but emerging technologies allow signal analyses that go far beyond the scoring rules for manual analysis of sleep recordings. These technologies may apply to the analysis of signals obtained in standard polysomnography in addition to novel signals more recently developed that provide both direct and indirect measures of sleep and breathing in the ambulatory setting. Automated analysis of signals such as electroencephalogram and oxygen saturation, in addition to heart rate and rhythm, provides a wealth of additional information on sleep and breathing disturbances and their potential for comorbidity.


Occupational violence in a tertiary emergency department: A retrospective descriptive study.
Occupational violence in emergency departments (EDs) impacts staff and patients. Most hospitals have a response mechanism called a 'Code Black' or similar. We aimed to determine the incidence of Code Black activations in a tertiary ED and describe contributory factors, management strategies and adverse events. Descriptive study in a tertiary ED in South-East Queensland in 2021. Adult patients for who a Code Black had been activated were eligible. Data were obtained from a prospectively collected Code Black database, supplemented with retrospective electronic medical records. There were 386 Code Black events. The incidence of Code Black activation was 11.0 per 1000 adult ED presentations. Individuals requiring Code Black activation were 59.6 % male with a mean age of 40.9 years. The primary diagnosis was mental illness related in 55.1 %. Alcohol was a suspected factor in 30.9 %. When Code Black activation occurred, median length of stay increased. Restraint including physical, chemical or both were used in 54.1 % of Code Blacks. Occupational violence occurs at a three-fold greater incidence within this ED than reported elsewhere. This study reinforces other literature suggesting an increase in occupational violence, demonstrating the need for dedicated preventative strategies for patients at risk of agitation.


Coated macroporous carriers with oxirane groups and their reactivity.
Macroporous carriers were prepared by coating controlled pore silicas with copolymers of hydroxyalkyl methacrylate and alkaline dimethacrylate activated by epichlorhydrin (140-1000 mumol/g epoxide group content). The relationship between the preparation conditions (the monomer ratio, the nature of the solvent, the method of activation by epichlorhydrin and the reaction temperature) was studied, as well as the surface characteristics responsible for the carrier's ability to bond (the value of the surface area before and after coating with copolymers and the degree of cross-linking required for the accessibility of the reactive groups). The coupling of various amino compounds, ammonia, aminopropanol, 1,2-diaminoethane, 1,6-diaminohexane and, as a model enzyme, alpha chymotrypsin on to derivatized carriers was investigated as a function of pH, reaction time and the concentration of the compound bonded.


The Anesthetic Implications of Aqueous Drainage Devices and Glaucoma: A Report of a Patient Undergoing Urgent Prone Cervical Decompression and Fusion.
The pathophysiology of glaucoma and perioperative visual loss is similar. A patient with glaucoma may be at increased risk of perioperative visual loss. For both, goals of management include optimizing ocular perfusion pressure and oxygen delivery. One treatment for refractory glaucoma is an aqueous drainage device; however, there is no published literature on the anesthetic management of patients with these devices. We present the case of a patient with recalcitrant glaucoma treated with an Ahmed Glaucoma Valve who underwent urgent prone surgery. Anesthetic implications of aqueous drainage devices and glaucoma are discussed, and recommendations are made.


Lessons from the Embryo: an Unrejected Transplant and a Benign Tumor.
Embryogenesis is regarded the 'miracle of life', yet numerous aspects of this process are not fully understood. As the embryo grows in the mother's womb, immune components, stem cells and microenvironmental cues cooperate among others to promote embryonic development. Evidently, these key players are frequently associated with transplantation failure and tumor growth. While the fields of transplantation and cancer biology do not overlap, both can be viewed from the perspective of an embryo. As an 'unrejected transplant' and a 'benign tumor', lessons from embryonic development may reveal features of transplants and tumors that have been overlooked. Therefore, eavesdropping at these natural complex events during pregnancy may inspire more durable approaches to arrest transplant rejection or cancer progression.


Predictors of thromboembolism during coil embolization in patients with unruptured intracranial aneurysm.
To identify the incidence of thromboembolic complications based on magnetic resonance imaging (MRI) and to explore the potential risk factors for thromboembolism (TE) during the periprocedural period of elective coil embolization for unruptured intracranial aneurysms. We retrospectively reviewed all aneurysm cases treated with coil insertion between January 2008 and March 2011. Two hundred eighty-two coiling procedures for unruptured aneurysms were included in this study. The patients' demographic characteristics were documented and records reviewed for abnormalities in diffusion-weighted imaging (DWI) seen on post-procedure MRI, intraoperative thrombus formation, and clinical signs of stroke. Overall, there were 87 (30.9 %) procedure-related complications in 282 aneurysms treated: 2 (0.7 %) procedural ruptures, 5 (1.8 %) symptomatic infarctions, and 80 (28.3 %) asymptomatic infarctions. Thromboembolic events during the procedure were observed more often in the the hyperlipidemia group (32/71 aneurysms, 45.1 %) than in the normal lipid profile group (39/196 aneurysms, 25.6 %; p = 0.002; chi-squre test). The coiling technique and size of the aneurysm were also associated with TE (p < 0.001 and p = 0.004). Hyperlipidemia seems to be associated with a significant increase in the rate of thromboembolic events. In preventive procedures, modifiable risk factors should be managed to reduce complications. Although permanent deficits are rare, the high rate of thromboembolic events suggests that improvements in the technique, such as the addition of antiplatelet agents and the development of new embolic materials, are necessary.


Venous gas bubble formation and decompression risk after scuba diving in persons with chronic spinal cord injury and able-bodied controls.
Prospective study. To evaluate the formation of venous gas bubbles following open-sea scuba dives in persons with chronic spinal cord injury (SCI) and in able-bodied diving instructors (C) and to assess the risk for decompression sickness (DCS). Field study at the Island of Krk, Croatia. Gas bubbles were monitored with an ultrasound scanner 40 min after surfacing. The probability of DCS (P((DCS))) was estimated from the recorded depth-time profile using a decompression model. Divers completed six dives in 3 days using a modified Bühlmann decompression model, and none developed signs of DCS. Mean P((DCS)) was similar in both groups, SCI (0.51+/-0.2%) and C (0.64+/-0.27%), and was seen to increase with subsequent dives. Number of bubbles (bubbles per cm(2)) was low in both groups on all 3 days of diving. We have used the P((DCS)) as a severity index of diving exposure. Overall, the severity of exposure in SCI subjects was consistent with the range of typical recreational dives, suggesting that the diving profile used is very safe.


Most of the field/inductive substituent effect works through the bonds.
An application of the quantum chemical modeling allowed to investigate the nature of the field/inductive substituent effect (SE). For this purpose, series of X-tert-butyl···tert-butane (TTX) complexes (where X = NMe2, NH2, OH, OMe, Me, H, F, Cl, CF3, CN, CHO, COMe, CONH2, COOH, NO2, NO) were studied. A starting distance between central carbon atoms in substituted and unsubstituted fragments of TTX, dC1-C4, was the same as the distance C1-C4 in X-substituted bicyclo[2.2.2]octane (BCO), where the SE acts both via bonds and via space. A strength of interaction between substituted and unsubstituted components of TTX was described by deformation and interaction energies. The substituent effect on electronic structure through the bonds and the space was characterized using charge of the substituent active region (cSAR) approach. The comparison of the SE characteristics obtained for alicyclic BCO and for TTX complexes document a significantly stronger field/inductive effect through bonds than through space.


Overexpression of conserved dopamine neurotrophic factor (CDNF) in astrocytes alleviates endoplasmic reticulum stress-induced cell damage and inflammatory cytokine secretion.
Astrocyte damage and the disorders of cytokine secretion induced by endoplasmic reticulum stress (ERS) are crucial pathological processes in ischemic injury of the central nervous system (CNS), (e.g., ischemic reperfusion injury of the brain and spinal cord). ERS stimulates damage to astrocytes and the release of pro-inflammatory cytokines, which deteriorates CNS injury. This current study investigates whether the overexpression of conserved dopamine neurotrophic factor (CDNF) alleviates ER stress-induced cell damage and inflammatory cytokine secretion. We found that primary astrocytes showed both a successful transduction and a significant overexpression of CDNF protein following lentivirus application. Our results show that the percentage of LDH released as a result of ER stress was significantly lower in astrocytes with an overexpression of CDNF than in the control groups without CDNF overexpression, indicating that CDNF alleviates ER stress-induced astrocyte damage. The secretion and mRNA expression levels of pro-inflammatory cytokines were increased by tunicamycin, and this stimulation was significantly suppressed by an overexpression of CDNF, demonstrating that CDNF plays an important role in astrocyte inflammation and functioning by resisting ER stress. These findings suggest that primary astrocytes can be efficiently transduced with CDNF lentiviral vectors and that the overexpression of CDNF in astrocytes shows the potential to alleviate cell damage and proinflammatory cytokine secretion, which may represent a promising strategy for neuroprotection in the CNS.


Using climate-driven leaf phenology and growth to improve predictions of gross primary productivity in North American forests.
Forest ecosystems are an important sink for terrestrial carbon sequestration. Hence, accurate modeling of the intra- and interannual variability of forest photosynthetic productivity remains a key objective in global biology. Applying climate-driven leaf phenology and growth in models may improve predictions of the forest gross primary productivity (GPP). We used a dynamic non-structural carbohydrates (NSC) model (FORCCHN2) that couples leaf development and phenology to investigate the relationships among photosynthesis and environmental factors. FORCCHN2 simulates spring and autumn phenological events from heat and chilling, respectively. Leaf area index data from satellites along with climate data estimated localized phenological parameters. NSC limitation, immediate temperature, accumulated heat, and growth potential comprised a daily leaf-growth model. Functionally, leaf growth was decoupled from photosynthesis. Leaf biomass determined overall photosynthetic production. We compared this model with outputs of the other six terrestrial biospheric models and with observations from the North American Carbon Program Site Interim Synthesis in 18 forest sites. This model improved the predicted performance of yearly GPP with a 57%-210% increase in correlation (median) and up to a 102% reduction in biases (median), compared to three prognostic models and three prescribed models. At the North America continental scale, the model predicted the average annual GPP of 7.38 Pg C/year from forest ecosystems during 1985-2016. The results showed an increasing trend of GPP in North America (1.0 Pg C/decade). The inclusion of climate-driven phenology and growth has a significant potential for improving dynamic vegetation models, and promotes a further understanding of the complex relationship between environment and photosynthesis.


Sarcoidosis presenting as facial and scalp ulceration with secondary bacterial infection of the skin.
A 67-year-old man with a medical history of multiorgan sarcoidosis was admitted to the hospital with skin ulceration and a superimposed polymicrobial infection that had failed outpatient management. The patient's outpatient regimen included doxycycline, ciprofloxacin and moderate-dose prednisone therapy for a coinfection with Pseudomonas aeruginosa and methicillin-susceptible Staphylococcus aureus The patient presented after a syncopal episode initially thought to be due to severe dehydration. Owing to concern for cardiac sarcoidosis as well as worsening skin lesions, he was admitted to the hospital for cardiac monitoring and intravenous antibiotics. On admission, we broadened antibiotic coverage and initiated high-dose steroids at 1 mg/kg/day of prednisone. He was discharged on intravenous antibiotics and a slow steroid taper 3 days later. At the patient's 1-month and 5-month follow-up clinic visits, he demonstrated remarkable improvement of his scalp and facial wounds.


Accuracy of Devereaux and Teichholz formulas for left ventricular mass calculation in different geometric patterns: comparison with cardiac magnetic resonance imaging.
Left ventricular (LV) myocardial mass is important in the evaluation of cardiac remodeling and requires accurate assessment when performed on linear measurements in two-dimensional echocardiography (Echo). We aimed to compare the accuracy of the Devereaux formula (DEV) and the Teichholz formula (TEICH) in calculating LV myocardial mass in Echo using cardiac magnetic resonance (CMR) as the reference method. Based on preceding mathematical calculations, we identified primarily LV size rather than wall thickness as the main source of bias between DEV and TEICH in a retrospective derivation cohort (n = 1276). Although LV mass from DEV and TEICH were correlated with CMR, TEICH did not show a proportional bias as did DEV (- 2 g/m2 vs. + 22 g/m2). This could be validated in an independent prospective cohort (n = 226) with symptomatic non-ischemic heart failure. DEV systematically overestimated LV mass in all tiers of LV remodeling as compared to TEICH. In conclusion, the TEICH method accounts for the changes in LV geometry with increasing LV mass and thus better reflects the different pattern of LV remodeling than the DEV method. This has important clinical implications, as TEICH may be more appropriate for use in clinical practice, rather than DEV, currently recommended.


Selective ingestion and response by Daphnia magna to environmental challenges of microplastics.
Our current understandings of the effects of microplastics and nanoplastics (MNPs) on aquatic animals are predominantly based on the single types of plastic particles. In the present study, we employed the highly fluorescent MNPs that incorporated aggregation-induced emission fluorogens and investigated the selective ingestion and response of Daphnia exposed to different types of plastics at environmentally relevant concentrations simultaneously. When daphnids were exposed to a single MNP, D. magna ingested them instantly in significant amounts. However, even low concentrations of algae had a significant negative impact on the MNP uptake. Specifically, algae caused the MPs to pass through the gut faster, reduced acidification and esterase activity, and changed the distribution of MPs in the gut. In addition, we also quantified the influences of size and surface charge on the selectivity of D. magna. The daphnids selectively ingested larger and positively charged plastics. MPs effectively reduced the uptake of NP and increased its gut passage time. Aggregation of positively and negatively charged MNPs also influenced the gut distribution and increased the gut passage time. The positively charged MPs accumulated in the middle and posterior gut, while aggregation of MNPs also increased acidification and esterase activity. These findings provided fundamental knowledge on the selectivity of MNPs and the microenvironmental responses of zooplankton guts.


Hepatitis C virus in the etiology of chronic hepatitis and liver cirrhosis: possibility of mixed viral infections due to parenteral transmission.
Sera obtained from 381 patients with chronic liver disease from four cities within the USSR were studied for HBV, HDV, and HCV markers of infection. Anti-HCV activity was detected in 41.2% of non-A, non-B cases. The etiological distribution of chronic hepatitis in Moscow and Dushanbe was similar with an approximate 20% prevalence for HBV, HDV, and HCV infections, whereas in Yakutsk 40% of cases were caused by HDV infections. The etiology of disease remained unrecognized in approximately 40% of patients with chronic liver disease in Moscow and Dushanbe and in 15% in Yakutsk. Anti-HCV activity was detected in 18.8% of patients with chronic HBV infections and in 8.3% of patients with chronic HDV infections. Anti-HCV activity was detected in 41% of patients without markers of HBV or HDV infections. The reasons for the observed differences in HCV prevalence among patients chronically infected with HDV are discussed.


The role of obstructive sleep apnea on the prognosis of pulmonary embolism: a systemic review and meta-analysis.
The relationship between obstructive sleep apnea (OSA) and pulmonary embolism (PE) has been reported by some studies but the underlying mechanism remains unclear. We aimed to systematically assess the role of OSA on the disease prognosis of PE. We searched for studies on the relationship of OSA and the prognosis of PE published up to February 2020 among PubMed, Web of Science, EMBASE, and Cochrane Library databases. Two independent reviewers conducted the process of study search and screening, quality assessment, and data extraction. Meta-analysis was carried out using RevMan 5.3. A total of 9 articles were included, and the funnel plots suggested no evidence of publication bias among studies. The results showed that compared to PE patients without OSA, the PE patients with moderate-severe OSA were more likely to be high-risk type (OR = 1.96, 95% CI [1.14, 3.34]) and with higher index of disease severity (sPESI: OR = 2.29, 95% CI [1.50, 3.47]; PAOI%: MD = 13.52, 95% CI [7.2, 19.83]). The prevalence of recurrent PE was higher in PE patients with OSA than those without OSA (RR = 3.87, 95% CI [1.65, 9.07]). However, there was no significant difference in right ventricle to left ventricle short-axis diameter (MD = 0.08, 95% CI [- 0.06, 0.21]), length of hospital stay (MD = 1.03, 95% CI [- 1.11, 3.17]), or prevalence of deep vein thrombosis (OR = 0.87, 95% CI [0.48, 1.57]). Sensitivity and subgroup analysis showed that the pooled outcomes were stable. OSA, especially moderate-severe OSA, was a risk factor for high-risk PE and recurrent PE. However, the current evidence showed that the length of hospital stay is not influenced by OSA.


Dynamic contrast-enhanced MR imaging of uterine endometrial carcinoma with/without squamous differentiation.
Endometrial carcinoma with strong enhancement on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is suggestive of high-grade type II endometrial carcinoma. However, low-grade type I endometrial carcinoma may also sometimes show strong enhancement. We hypothesized that squamous differentiation would contribute to the strong enhancement at the early phase on DCE-MRI-like uterine cervical squamous cell carcinoma and compared the DCE-MRI findings of endometrial carcinoma with and without squamous differentiation. DCE-MRI of endometrial carcinoma including 41 low-grade type I endometrial carcinomas without squamous differentiation (LG), 39 low-grade type I endometrial carcinomas with squamous differentiation (LGSD), and 20 high-grade type II endometrial carcinomas (HG) was retrospectively evaluated. Significant difference in the time-intensity curves was found between LG and HG and LG and LGSD, whereas no significant difference was seen between HG and LGSD. Curve type 3 (initial signal rise which is steeper than that of the myometrium) was more frequent in HG (60%) and LGSD (77%) than in LG (34%). It should be recognized as a pitfall that high-grade type II endometrial carcinoma and low-grade type I endometrial carcinoma with squamous differentiation may show similar early strong enhancement on DCE-MRI.


The amniotic band syndrome: a possible complication of amniocentesis.
Malformations of the upper distal extremities were noted in an otherwise healthy infant whose mother underwent diagnostic amniocentesis. A causal relationship is postulated.


The Value of Impulse Oscillometric Parameters and Quantitative HRCT Parameters in Differentiating Asthma-COPD Overlap from COPD.
To evaluate the value of impulse oscillometry (IOS) and quantitative HRCT parameters for differentiating asthma-COPD overlap (ACO) in COPD patients. We enrolled 44 controls and 66 COPD patients, divided into the pure COPD group (n=40) and the ACO group (n=26). Spearman correlation analysis was utilized to assess the relationship between the quantitative HRCT and IOS parameters. A binary logistic regression analysis was performed to analyze the associations between the different variables and the risk of ACO. Receiver operating characteristic (ROC) curves were employed to identify the optimal cutoff and assess the diagnostic value of relative volume change -856 HU to -950 HU (RVC-856 to -950), decrease in the resistance from 5 Hz to 20 Hz (R5-R20) and their combination in predicting ACO. Bootstrapping validation was used to evaluate the internal validation. The concordance index (C-index) and calibration plot were calculated to assess the discrimination and calibration of the prediction model. Binary logistic regression analysis indicated that RVC-856 to -950 and the IOS parameters (R5-R20, R5, X5) were independently correlated with a higher risk of developing ACO after adjusting for age, sex, body mass index (BMI), history of smoking, exacerbation and atopy or allergic rhinitis. A correlation analysis showed a good correlation between the pulmonary function parameters and RVC-856 to -950, with a weaker correlation with the % area of low attenuation (LAA%) in ACO patients. Combining RVC-856 to -950 and R5-R20 to predict ACO, the AUC was 0.909, and the optimal cutoff value was >-0.62 for RVC-856 to -950 and >0.09 for R5-R20. Good calibration and favorable discrimination were displayed with a higher C-index. More serious small airway impairment exists in ACO patients. The combination of RVC-856 to -950 and R5-R20 could be applied to differentiate ACO from COPD patients.


Identifying missing links in the conceptualization of financial toxicity: a qualitative study.
Financial toxicity can have a major impact on the quality of life of cancer survivors but lacks conceptual clarity and understanding of the interrelationships of the various aspects that constitute financial toxicity. This study aims to extract major drivers and mediators along the pathway from cancer-related costs to subjective financial distress from the patients' experiences to establish a better understanding of financial toxicity as a patient-reported outcome. Qualitative semistructured interviews with 39 cancer patients were conducted in Germany and addressed patient experiences with cancer-related financial burden and distress in a country with a statutory health care system. Transcripts were analyzed using content analysis. Several aspects of financial burden need to be considered to understand financial toxicity. The assessment of the ability to make ends meet now or in the future and the subjective evaluation of financial adjustments-namely, the burden of applied financial adjustments and the availability of financial adjustment options-mediate the connection between higher costs and subjective financial distress. Moreover, bureaucracy can influence financial distress through a feeling of helplessness during interactions with authorities because of high effort, non-traceable decisions, or one's own lack of knowledge. We identified four factors that mediate the impact of higher costs on financial distress that should be addressed in further studies and targeted by changes in policies and support measures. Financial toxicity is more complex than previously thought and should be conceptualized and understood more comprehensively in measurements, including the subjective assessment of available adjustment options and perceived burden of financial adjustments.


Overnight polygraphic studies of infantile spasms--influence of hormone therapy on sleep states, pulse, respiration and seizure activities.
The influence of hormone therapy on sleep states, pulse, respiration and seizure activities of infantile spasms was examined by means of overnight sleep polygraphy. Also the correlation between the changes of these parameters and the prognosis was investigated. The results were as follows: 1) In all cases, the awake time of TIB during hormone therapy was longer than before hormone therapy. The reduction of REM sleep time of SPT and lowering of REM density were remarkable during hormone therapy in cases with delayed psychomotor development as compared with cases with a considerable degree of psychomotor development. During hormone therapy, the NREM sleep time of SPT was shortened in cases with ACTH therapy, and prolonged in case with hydrocortisone therapy. 2) During hormone therapy, the pulse rate increased significantly in cases with a considerable degree of psychomotor development, but decreased significantly in cases with delayed psychomotor development. The change of respiratory rate by hormone therapy was not remarkable in all cases. 3) In cases with hypsarhythmic EEG records, the number of spikes decreased drastically by hormone therapy. In the case with EEG record of focal spikes, the number of spikes increased by hormone therapy. From the results mentioned above, the mechanism for effectiveness of hormone therapy and correlation between the administration of hormone therapy and prognosis was discussed.


Evolving microbial patterns of acute mastoiditis in pediatric patients undergoing mastoidectomy.
To investigate the microbial patterns and clinical outcomes of pediatric patients undergoing mastoidectomy for acute coalescent mastoiditis and to identify factors associated with poor outcomes and/or prolonged treatment. Monocentric retrospective cohort study. Tertiary referral pediatric hospital in Indiana. By cross-referencing database data from the Pediatric Health Information System (PHIS) querying for all inpatient stays (patients younger than eighteen) with a diagnostic code of mastoiditis between January 1st, 2010 and August 31, 2019, and the electronic health record (Cerner) for Riley Hospital for Children, 46 patients with mastoidectomy were included. A two-tailed T-test was used to evaluate continuous parametric data. Statistical significance was determined as P < 0.05. For continuous variables, data was analyzed using continuous logistic regression. A criteria of p > 0.1 was used for inclusion in the multivariate regression. Inclusion criteria was met by 46 patients. From 2010 to 2019, S. pyogenes and S. pneumoniae were the most common bacteria, each isolated in 11 of 42 bacterial isolates (26.2%). There was no growth in 35.4% (17/48) of intra-operative wound cultures. On univariate analysis, patients with negative cultures had longer length of hospital stay (LOS) (7.7 days [6.5] vs. 4.3 [2.8]; p = 0.018) as well as higher rates of PICC (peripherally inserted central catheter) placement (53.3% vs. 19.4%; p = 0.021). There was a statistically significant difference in terms of gender (p = 0.021), with 15 males and 16 females in the positive culture cohort and 13 males and 2 females in the negative culture cohort. On multivariate analysis, which included gender, PICC placement, both intracranial and extracranial complications, duration of antibiotics, and LOS, female gender was the only significant predictor of positive culture status (p = 0.039). S. pyogenes and S. pneumoniae were the predominant etiologic agents in acute coalescent mastoiditis between 2010 and 2019, and negative wound cultures were associated with worse clinical outcomes.


Humoral Mediators of Remote Ischemic Conditioning: Important Role of eNOS/NO/Nitrite.
Remote ischemic conditioning (RIC) is a powerful cardioprotectant and neuroprotectant. The mechanism of protection likely involves circulating, blood-borne mediators that transmit the signal from the periphery to the brain. The neuroprotective effect of RIC may be partially related to improvements in cerebral blood flow (CBF). Nitrite is a key circulating mediator of RIC and may be a mediator of increased CBF and also mediate cytoprotection through its effects on nitrosylation of mitochondrial proteins such as complex I. Measuring plasma nitrite may serve as an important blood biomarker, and measuring CBF by techniques such as MRI arterial spin labeling (ASL) may be an ideal surrogate imaging biomarker in clinical trials of RIC.


Onset of androgen action in MCF-7 human breast cancer cells is not accompanied by receptor depletion.
Quantitative and qualitative changes in estrogen receptor follow addition of estradiol to estrogen responsive MCF-7 human breast cancer cells. We asked whether similar changes would accompany treatment of these cells with physiologically relevant concentrations of androgens. Androgen receptor sites were quantified by competitive protein binding assays on whole cells or extracts at various times following hormone addition. Both direct and exchange assays were employed. The androgen receptor in all of these experiments remained in a form which is completely exchangeable and approx 85% salt extractable. Quantity of receptor was unchanged (30,000 sites/cell, Kd 0.1 nM). Responsiveness to hormone treatment was demonstrated by antagonizing the estrogen dependent augmentation of cytoplasmic progesterone receptor in the MCF-7 cells with androgens. Thus, the androgen receptor was shown to be biologically active, but no time dependent quantitative or qualitative changes were observed during the first 6 h following androgen treatment.


The impact of climatic factors and host density on the long-term population dynamics of vole helminths.
The seasonal and long-term population dynamics of helminths parasitizing voles suggested that density-dependent factors might be important in the population dynamics of common species, whereas density-independent factors predominate in the regulation of the rare species. To test this, we used single and multiple regression to analyse the effects of climatic factors and host density on populations of six species of vole helminths over 12 years. The data do support the idea of a difference between common and rare species of helminths, but they clearly do not support the above hypothesis. The common helminths Heligmosomum mixtum (Nematoda) and Catenotaenia sp. (Cestoda) responded to changes in temperature sum (>5° C days) and precipitation during summer. The combined effect of climatic factors and host density explained most of the variation in the long-term dynamics of these common species. By contrast, the long-term dynamics of the rare helminths Paranoplocephala kalelai (Cestoda), Mastophorus muris, Capillaria sp. and Syphacia petrusewiczi (Nematoda) were explained less well by weather and host density than those of the common ones. Furthermore, the common and rare helminths differed in some ways in their responses to climatic factors.


Immunogenicity and safety of inactivated quadrivalent influenza vaccine compared with the trivalent vaccine for influenza infection: an overview of systematic reviews.
Influenza infection is a highly preventable transmissible viral disease associated with mild upper respiratory symptoms and more severe conditions such as lethal pneumonia. Studies have shown that a broader spectrum influenza vaccine could reduce influenza's burden of disease in low- and middle-income countries. A considerable number of systematic reviews reported that quadrivalent influenza vaccines are considered more effective compared to trivalent vaccines, hence, there is a need for an overview in order to synthesize the current evidence pertaining to the comparison between quadrivalent and trivalent inactivated influenza vaccines. The aim was to summarize the evidence from systematic reviews that investigated the immunogenicity and safety of the Influenza's inactivated quadrivalent vaccine (QIV) compared to the trivalent vaccine (TIV), in the general population. We searched articles up to December 2022 at: Web of Science, EMBASE, MEDLINE, Cochrane Library, and SCOPUS. The search strategy was conducted following the PICO model. We included systematic reviews comparing the primary outcomes of immunogenicity (seroprotection rate and seroconversion rate) and adverse events using risk ratios. The AMSTAR 2 and ROBIS were used for quality assessments, and GRADE was used for evidence certainty assessments. We included five systematic reviews, totalling 47,740 participants. The Quadrivalent Inactivated Influenza Vaccine (QIV) exhibited enhanced immunogenicity in the context of B-lineage mismatch when compared to the Trivalent Inactivated Influenza Vaccine (TIV). While the safety profile of QIV was found to be comparable to that of TIV, the QIV showed a higher incidence of solicited local pain among children and adolescents, as well as an increased frequency of local adverse events within the adult population. Our findings suggest that the QIV provides a superior immunogenicity response compared to the TIV in all age groups evaluated, especially when a lineage mismatch occurred. The safety of QIV was considered similar to the TIV, with no serious or systemic solicited or unsolicited adverse events; tough pain at the injection site was greater for QIV. We recommend caution owing to the high risk of bias in the selection process and no protocol registration.


Probabilistic public health risks associated with pesticides and heavy metal exposure through consumption of common dried fish in coastal regions of Bangladesh.
The chemical contaminants in dried fish are of great food safety concern and an emerging public health issue in Bangladesh. The aim of this study was to assess the public health risk associated with exposure to pesticides (organochlorine and organophosphorus) and heavy metals (lead, mercury, cadmium, chromium, arsenic) through the consumption of dried fish (Bombay duck, ribbon fish, silver jewfish, shrimp, Chinese promfret) in coastal districts (Cox's Bazar, Chittagong, Bhola, Patuakhali, Khulna) of Bangladesh. Dried fish consumption data were collected from 500 adult respondents (100 from each district) using a food frequency questionnaire (FFQ). Pesticide residues were determined using QuEChERS extraction coupled to gas chromatography and gas chromatography mass spectrometry, and heavy metals were estimated using an atomic absorption spectrophotometric method. The results revealed that the frequency and amount of dried fish consumption was highest for Bombay duck in Cox's Bazar (11.57 g/capita/day) and ribbon fish (12.10 g/capita/day) in Chittagong. The estimated daily intake (EDI, 7.40 × 10-5 to 1.10 × 10-4 mg/kg/day) and health risk index (HRI, 0.013 to 0.16) values expressed no health risk from pesticide residues in all the positive samples. For heavy metals, target hazard quotients (THQ) for non-carcinogenic health risk were below 1 (0.001-0.154), indicating no health risk for all samples. However, carcinogenic risk R value indicated a potential health risk for chromium (2.64 × 10-6 to 4.06 × 10-6), and carcinogenic RT value (2.82 × 10-6 to 5.71 × 10-6) indicated a potential health risk for all the metals. It is concluded that the risk of exposure to pesticides through the consumption of dried fish is low, while heavy metals pose moderate-to-high health risks to dried fish consumers in the study area. Thus, the study suggests an appropriate risk management policy that controls pesticides and heavy metals in dried fish to ensure safe food for local and global consumers, underpinned by a producers' capacity building and consumers' awareness raising strategy.


Impact of different scanners and acquisition parameters on robustness of MR radiomics features based on women's cervix.
MR Radiomics based on cervical lesions from one single scanner has achieved promising results. However, it is a challenge to achieve clinical translation. Considering multi-scanners and non-uniform scanning parameters from different centers in a real-world medical scenario, we should first identify the influence of such conditions on the robustness of MR radiomics features (RFs) based on the female cervix. In this study, 9 healthy female volunteers were enrolled and 3 kiwis were selected as references. Each of them underwent T2 weighted imaging in three different 3.0-T MR scanners with uniform acquisition parameters, and in one MR scanner with various scanning parameters. A total of 396 RFs were extracted from their images with and without decile intensity normalization. The RFs' reproducibility was evaluated by coefficient of variation (CV) and quartile coefficient of dispersion (QCD). Representative features were selected using the hierarchical cluster analysis and their discrimination abilities were estimated by ROC analysis through retrospective comparison with the junctional zone and the outer muscular layer of healthy cervix in patients (n = 58) with leiomyoma. This study showed that only a few RFs were robust across different MR scanners and acquisition parameters based on females' cervix, which might be improved by decile intensity normalization method.


RNA-Seq Analysis Reveals the Potential Molecular Mechanisms of Puerarin on Intramuscular Fat Deposition in Heat-Stressed Beef Cattle.
To investigate the effect of Puerarin on intramuscular fat deposition in heat-stressed beef cattle and its underlying mechanism. Thirty-two healthy Jinjiang bulls were randomly divided into four groups and dietary with 0 (Control), 200 (Pue200), 400 (Pue400), and 800 (Pue800) mg/kg Puerarin in the feed concentrate. The results showed that Puerarin treatment enhanced the concentration of crude fat, fatty acid (C14:1 and C17:1), and the activity of fatty acid synthase in Longissimus thoracis (LT), but decreased the levels of blood leptin (P < 0.05). High-throughput sequencing of mRNA technology (RNA-Seq) was used and the analysis showed that 492 genes were down-regulated and 341 genes were up-regulated in LT, and these genes were significantly enriched to the pathways related to lipid metabolism. These results indicated that dietary supplemental with Puerarin enhanced intramuscular fat deposition by regulating lipid metabolism of heat-stressed beef cattle.


Liolaemus duellmani Cei, 1978 (Reptilia: Squamata: Liolaemini), redescription of the holotype and variation in a microendemic and inadequately known species of Liolaemus from Northwestern Patagonia.
Liolaemus duellmani is a microendemic lizard described from southern Mendoza, Argentina, representing the southernmost distribution of the Liolaemus montanus species group. The original description was based on a small batch of preserved material and a juvenile collected alive. Along the years, this poorly known species was rarely collected or observed in the field, with no additional reports or findings published until a recent description of an adult female which was considered as a rediscovery of the species. Here, we redescribe the species and describe variation on external morphology, coloration, and some natural history observations.


High-dose radiation-resistant lung cancer cells stored many functional lipid drops through JAK2/p-STAT3/FASN pathway.
The understanding of radiation resistance is still unclear. This study aims to explore the new mechanism of radiation resistance in lung cancer from the perspective of lipid metabolism. Oil red O was used to detect the amount of lipid droplets in high-dose radiation-resistant lung cancer cells (HDRR-LCCs) and the primary lung cancer cells. Western blot analysis was used to determine the protein expression levels of key molecules related to de novo fatty acid synthesis and fatty acid transport. Orlistat was used to inhibit the de novo fatty acid synthesis. The prediction of the transcriptional regulators of fatty acid synthetase (FASN) was analyzed by bioinformatics. AZD-1480 was used to inhibit the JAK2/STAT3 pathway to observe its effects on FASN and intracellular lipid droplets. The regulation of the transcription factor p-STAT3 on the FASN gene was verified by Chip-qPCR. Finally, we used the public data of lung cancer patients to analyze the correlation between FASN and LPL gene expression with the prognosis. There were more lipid drops in the HDRR-LCCs than in the primary lung cancer cells. HDRR-LCCs preferred de novo synthesis of fatty acids, and high expression of LPL homodimers indicated a high intake of extracellular fatty acids. The expression of FASN was increased in HDRR-LCCs compared with the primary lung cancer cells in a radiation-dose-dependent way, while LPL homodimers did not show such a trend. The lipid droplets, cell proliferation, and radiation resistance were decreased in HDRR-LCCs after orlistat treatment. Lipid droplets were significantly reduced, and the protein expression of FASN also decreased when using AZD-1480 to inhibit the JAK2/STAT3 pathway. The Chip-qPCR showed that p-STAT3 was the upstream regulator which binds to the promoter region of FASN. Survival analysis showed that high expression of the FASN gene was associated with a poor prognosis in lung cancer patients who received radiotherapy. Our studies discovered that lipids deposited in HDRR-LCCs were due to endogenous de novo fatty acids synthesis and exogenous lipids uptake. JAK2/p-TAT3/FASN could be used as promising targets for radiotherapy sensitization. Our study provided a new theoretical basis for studying the mechanism of radiation resistance in lung cancer.


Clinical features of autosomal dominant retinitis pigmentosa with rhodopsin gene codon 17 mutation and retinal neovascularization in a Japanese patient.
A 49-year-old Japanese man had autosomal dominant retinitis pigmentosa with a point mutation in codon 17 of the rhodopsin gene, resulting in a threonine-to-methionine change, and retinal neovascularization in both eyes. Pigmentary degeneration mainly in the inferior area of the fundus, and severe loss in the upper portion of the visual field were observed. Moderately preserved rod and cone functions were demonstrated by electroretinograms. These findings differed from those of Japanese and white patients with autosomal dominant retinitis pigmentosa with a codon 347 mutation and were almost the same as those of white patients with the codon 17 mutation. Our study indicates that phenotypic similarities exist among patients with the same mutation, but of different racial backgrounds. The neovascularization in the right eye diminished over a two-year period in conjunction with the progression of retinal degeneration.


Biodegradation and detoxification of organophosphate insecticide, malathion by Fusarium oxysporum f. sp. pisi cutinase.
Efficiencies of two lypolytic enzymes (fungal cutinase and yeast esterase) in malathion degradation were investigated. Surprisingly, degradation rate of malathion by fungal cutinase was very high, i.e. almost 60% of initial malathion (500 mg l(-1)) was decomposed within 0.5 h, and nearly 50% of the degraded malathion disappeared within initial 15 min. With the yeast esterase, despite the same concentration, more than 65% of malathion remained even after 2-day treatment. During enzymatic degradation of malathion, two malathion-derived compounds were detected, and time-course changes in composition were also monitored. In the degradation by both fungal cutinase and yeast esterase, two additional organic chemicals were produced from malathion: malathion monoacid (MMA) and malathion diacid (MDA) by ester hydrolysis. Final chemical composition after 2 d was significantly dependent on the enzyme used. Fungal cutinase produced MDA as a major degradation compound. However in the malathion degradation by yeast esterase, an isomer of MMA was produced in abundance in addition to MDA. Toxic effects of malathion and its final degradation products were investigated using various recombinant bioluminescent bacteria. As a result, the degradation products (including MMA) by esterase severely caused membrane damage and inhibition of protein synthesis in bacterial cells, while in the fungal cutinase processes, malathion was significantly degraded to non-toxic MDA after the extended period (2 days).


Microfluidic preparation of a novel phoxim nanoemulsion pesticide against Spodoptera litura.
With continuous development of pesticide dosage forms, emulsifiable concentrates using large amounts of organic solvents are gradually obsoleted. Nanoemulsions with high water content have been developed and the preparation processes also evolved, but these processes still exist some problems, such as poor controllability and high energy consumption. Microfluidic is a controllable nanoemulsion preparation system which mainly applied to pharmaceutical synthesis. In this study, the pesticide phoxim nanoemulsion was prepared by microfluidic technology. The optimized formulation of phoxim nanoemulsion was composed of Tween 80 and pesticide emulsifier 500 as surfactant, hexyl acetate as oil, and n-propanol as co-surfactant. Moreover, when the flow rates of water and oil in the microfluidic system were adjusted to 5 μL/min and 20 μL/min, phoxim nanoemulsion was obtained with a cloud point/boiling point of 109 °C, a particle size of 21.5 ± 0.8 nm and a potential value of - 18.7 ± 0.6 mV. Furthermore, the nanoemulsion had a rapid release effect in vitro which could be fitted by the Ritger-Peppas model. The feeding toxicity of the phoxim nanoemulsion was higher than that of commercial formulation while the contact killing effect was higher than that of the active ingredient. Therefore, pesticide dosage was reduced and the insecticidal effect was enhanced by using phoxim nanoemulsions. These results also confirm the potential of microfluidics as a green process to produce pesticide nanoemulsions.


Secondary-care treatment patterns in the UK for women with urinary incontinence.
To describe the treatment trends for women with urinary incontinence (UI) after their referral from primary to secondary care, as despite the high prevalence of UI within the female population, relatively few women actively seek treatment for their UI and fewer reach secondary care. We retrospectively reviewed the notes of patients attending in two randomly selected months in five hospital sites in the UK. Records were identified through outpatient clinic lists, surgery lists, nursing and physiotherapy lists. Data were collated and analysed for trends. In all, 412 women (mean age 54.6 years, SD 12.6) covering 1406 visits to secondary care were covered by the study. Most women had a symptomatic diagnosis of mixed UI and mild to moderate UI, as defined by their physician. Most women had conservative therapies by either continence nurses or physiotherapists, regardless of the severity of their condition; 73% had cystometry and 39% were recommended for surgical intervention. Women largely undergo similar procedures in secondary care. Most present with mixed UI. The perceived severity of disease did not preclude a trial of conservative therapies.


Localization of the oncogene c-erbA1 immediately proximal to the acute promyelocytic leukaemia breakpoint on chromosome 17.
Using in situ hybridization, c-erbA1 has been mapped immediately distal to the translocation breakpoint on chromosome 17 in fibroblasts with a karyotype 46,XX, t(15;17)(q22;q11). Previous work has shown that c-erbA1 is proximal to the translocation breakpoint on chromosome 17 in the t(15;17)(q22;q12-21) in acute promyelocytic leukaemia. The oncogene can therefore be localized to the region of chromosome 17 between the breakpoints in 17q11 and 17q12-21.


Immunogenicity of N-(2-hydroxypropyl)-methacrylamide copolymers--potential hapten or drug carriers.
After repeated i.p. immunizations of mice with 10 micrograms of homopolymer poly (HPMA) no antibodies were detected by the ELISA test. Immunization with copolymer P-Acap-Leu-HMDA leads to a weak antibody response, while immunization with a copolymer with some side chains modified with ARS or FITC groups (P-Acap-Leu-HMDA-ARS or P-Acap-Leu-HMDA-FITC) leads to a significant antibody response detectable by PFC, ELISA and haemagglutination tests. Most of these antibodies are aimed against the modifying haptenic group, a smaller amount against side oligopeptide sequences of the carrier. Intensity of the antibody response depends on: 1) the antigen dose--the optimal dose was 10 micrograms: both the higher (100 micrograms) and the lower doses (1 and 0.1 micrograms) induced considerably lower antibody responses; 2) molar mass of the immunizing fractions--fractions of high molar mass induced up to five times higher responses than those of a low molar mass; 3) the bound haptenic group--the ARS-copolymers induced ten times lower response than the FITC-copolymers. We detected no difference between capacities of the H-2a, H-2b and H-2d haplotypes to react with anti-ARS antibodies after immunization with P-Acap-Leu-HMDA-ARS.


Comparison of induced versus non-induced labor in post-term pregnancy. A randomized prospective study.
To determine the proper management of pregnancy in uncomplicated cases going beyond 42 weeks. Randomized controlled trial of induction of labor at or shortly after the 42-week limit, versus close monitoring without induction except when indicated for medical reasons. Hospital's obstetrical department 188 pregnant women, randomly allocated to two groups with 94 in each. Induction of labor by stripping of membranes and i.v. oxytocin infusion, with artificial rupture of membranes when the cervical opening was 3 cm or more in diameter. The control group was followed with clinical, biochemical and electronic tests, intervention being applied according to needs. Frequency and modes of operative delivery, maternal and perinatal morbidity and mortality. The distribution of gestational age (in weeks) at birth was almost identical in the two groups, but there were more operative deliveries in the control group than in the induction group (64 versus 48, p less than 0.05). Maternal complications and perinatal morbidity rates were equally distributed between the groups. There was one perinatal death in the induction group and two deaths among the controls. With due reservation for small numbers, routine induction after term may result in fewer operative deliveries. No other advantage has been demonstrated when compared with close monitoring and intervention when medically indicated.


Premature baby with extreme hyponatraemia (95 mmol per litre): a case report.
Whilst mild neonatal hyponatraemia is common and relatively harmless, extreme hyponatraemia of 95 mmol per litre has never been reported in a premature baby and such a level could be associated with immediate as well as long-lasting detrimental effects on health. Twenty-four days old baby boy born at 28 weeks gestation (triplet one) unexpectedly became moribund with hypovolaemic shock and was found to have blood sodium of 95 mmol per litre. Diagnostic work up revealed a combination of a urinary tract infection, inadvertently low sodium provision with donor breast milk, and weak renin-angiotensin-aldosterone response. Commencement of treatment with intravenous fluids and extra sodium led to unanticipated diuresis and faster than expected increase of sodium level. Ultimately, treatment resulted in clinical recovery and normalisation of sodium level, which subsequently remained normal with no additional sodium supplementation. Follow up revealed mild spastic diplegia. Continuous monitoring and daily medical reviews may not be sensitive enough to recognise development of extreme hyponatraemia. Blood sodium levels should be monitored closely and any abnormalities promptly addressed. Treatment of hypovolaemic hyponatraemia should be centred on fluid resuscitation, anticipation of "paradoxical" diuresis, and blood sodium correction rate of 8 to 10 mmol per litre per day.


Cutaneous allodynia as predictor for treatment response in chronic migraine: a cohort study.
Central sensitisation is an important mechanism in migraine chronification. It is presumed to occur in second and third order neurons sequentially, resulting in an analogous spatial distribution of cutaneous allodynia with cephalic and extracephalic symptoms. We investigated whether allodynia, and its subtypes based on spatial distribution and type of stimulus, predict response to treatment in chronic migraine patients. This study was conducted as part of the CHARM study (NTR3440), a randomized, double-blind, placebo-controlled trial in chronic migraine patients with medication overuse. We included 173 patients. The presence of cutaneous allodynia at baseline was established with the Allodynia Symptom Checklist. Primary endpoint was reversion from chronic to episodic migraine. Of all patients, 74.6% reported cutaneous allodynia. Absence of allodynia compared to presence of allodynia was predictive for reversion from chronic to episodic migraine, odds ratio (OR): 2.45 (95% CI: 1.03-5.84), p = 0.042. The predictive value was more pronounced when subdivided for spatial distribution, for participants without allodynia versus cephalic (OR: 4.16 (95% CI: 1.21-14.30), p = 0.024) and extracephalic (OR: 7.32 (95% CI: 1.98- 27.11), p = 0.003) allodynia. Mechanical, but not thermal, allodynia, was associated with outcome. Cutaneous allodynia, an important marker for central sensitization, likely has predictive value for treatment response in chronic migraine.


Clinical teaching as part of continuing professional development: Does teaching enhance clinical performance?
Physicians identify teaching as a factor that enhances performance, although existing data to support this relationship is limited. To determine whether there were differences in clinical performance scores as assessed through multisource feedback (MSF) data based on clinical teaching. MSF data for 1831 family physicians, 1510 medical specialists, and 542 surgeons were collected from physicians' medical colleagues, co-workers (e.g., nurses and pharmacists), and patients and examined in relation to information about physician teaching activities including percentage of time spent teaching during patient care and academic appointment. Multivariate analysis of variance, partial eta squared effect sizes, and Tukey's HSD post hoc comparisons were used to determine between group differences in total MSF mean and subscale mean performance scores by teaching and academic appointment data. Higher clinical performance scores were associated with holding any academic appointment and generally with any time teaching versus no teaching during patient care. This was most evident for data from medical colleagues, where these differences existed across all specialty groups. More involvement in teaching was associated with higher clinical performance ratings from medical colleagues and co-workers. These results may support promoting teaching as a method to enhance and maintain high-quality clinical performance.


Routine chest x-rays in intensive care units: a systematic review and meta-analysis.
Chest x-rays (CXRs) are the most frequent radiological tests performed in the intensive care unit (ICU). However, the utility of performing daily routine CXRs is unclear. We searched Medline and Embase (1948 to March 2011) for randomized and quasi-randomized controlled trials (RCTs) and before-after observational studies comparing a strategy of routine CXRs to a more restrictive approach with CXRs performed to investigate clinical changes among critically ill adults or children. In duplicate, we extracted data on the CXR strategy, study quality and clinical outcomes (ICU and hospital mortality; duration of mechanical ventilation and ICU and hospital stay). Nine studies (39,358 CXRs; 9,611 patients) were included in the meta-analysis. Three trials (N = 870) of moderate to good quality provided information on the safety of a restrictive routine CXR strategy; only one trial systematically assessed for missed findings. Pooled data from trials showed no evidence of effect of a restrictive approach on ICU mortality (risk ratio [RR] 1.04, 95% confidence interval [CI] 0.84 to 1.28, P = 0.72; two trials, N = 776), hospital mortality (RR 0.98, 95% CI 0.68 to 1.41, P = 0.91; two trials, N = 259), ICU length of stay (weighted mean difference [WMD] -0.86 days, 95% CI -2.38 to 0.66 days, P = 0.27; three trials, N = 870), hospital length of stay (WMD -2.50 days, 95% CI -6.62 to 1.61 days, P = 0.23; two trials, N = 259), or duration of mechanical ventilation (WMD -0.30 days, 95% CI -1.48 to 0.89 days, P = 0.62; three trials, N = 705). Adding data from six observational studies, one of which systematically screened for missed findings, gave similar results. This meta-analysis did not detect any harm associated with a restrictive chest radiograph strategy. However, confidence intervals were wide and harm was not rigorously assessed. Therefore, the safety of abandoning routine CXRs in patients admitted to the ICU remains uncertain.


Tracking of Cardiorespiratory Fitness and Physical Activity from Youth to Young Adulthood: Findings from the Prospective Special Turku Coronary Risk Factor Intervention Project (STRIP).
Using data from the Special Turku Coronary Risk Factor Intervention Project, cardiorespiratory fitness (rank-order correlation coefficient = 0.60-0.62) tracked stronger than physical activity (rank-order correlation coefficient = 0.27-0.38) between youth (age = 17 years) and young adulthood (age = 26 years). Cardiorespiratory fitness could help identify individuals at risk of maintaining poor fitness levels or developing adverse health in adulthood.


Unaltered immunocompetence in patients with non-disseminated breast cancer at the time of diagnosis.
Immunologic parameters were examined preoperatively in 104 patients with breast cancer, staged according to the TNM classification and in 95 age-matched healthy women. The immunologic evaluation in the peripheral blood included lymphocyte and monocyte counts, determination of E-rosette-forming T-lymphocytes (SER+) and B-lymphocytes (MER+), T-lymphocyte subsets defined with monoclonal antibodies (Leu-1, Leu-2a, Leu-3a) and with lectin fractionation (soybean agglutinin), lymphocyte transformation test with phytohemagglutinin (PHA) and concanavalin A (ConA), and colony formation of T-lymphocytes in agar (T-lymphocyte colony-forming cells, [TL-CFC]). Two age groups (Group A: 30-50 years; Group B: 51-70 years) and the different tumor stages (Stage I-IV) were analyzed. Patients and controls did not differ in the absolute numbers of lymphocytes, T- and B-cells. In patients of Group B, the absolute number of monocytes was increased slightly in Stage II and III and significantly in Stage IV (P less than 0.05). Similarly, the lymphocyte response to PHA was significantly reduced in Stage IV Group B only (P less than 0.05). ConA-induced lymphocyte proliferation and TL-CFC capacity were not different in patients and controls. In the small number of patients and age-matched controls in whom T-lymphocyte subsets were determined, the absolute numbers of T-cells with helper or suppressor phenotype as defined with Leu-3a, Leu-2a, or lectin fractionation with soybean agglutinin were similar. This study demonstrates that in patients with early breast cancer (Stage I-III), immunocompetence as defined by either functional in vitro studies or surface marker analysis is not significantly altered at the time of diagnosis. In contrast, patients with advanced disease (Stage IV) show a significant increase in the absolute number of monocytes and a depressed PHA responsiveness of mononuclear cells.


Amphotericin B containing microneedle ocular patch for effective treatment of fungal keratitis.
Topical application of poorly water-soluble antibiotics cannot achieve the desired therapeutic concentration within cornea. The purpose of this study was to fabricate, characterize and evaluate in-vivo effectiveness of amphotericin B (AmB) containing microneedle ocular patch (MOP) against fungal keratitis. MOP containing free or liposomal AmB was fabricated using micromolding technique to mimic contact lens. MOPs were prepared using dissolvable polymeric matrix including polyvinyl alcohol and polyvinyl pyrrolidone. AmB loaded MOP were studied for their physical and mechanical properties, drug loading and dissolution rate, corneal insertion and drug permeability. MOP loaded with 100 µg AmB had a compression strength of 35.1 ± 6.7 N and required an insertional force of 1.07 ± 0.17 N in excised human cornea. Ex-vivo corneal permeation studies revealed significant enhancement in AmB corneal retention with the application of MOP compared with free AmB or liposomal AmB application. Furthermore, AmB loaded MOP application significantly (P < 0.05) reduced the Candida albicans load within cornea as evaluated in both ex-vivo model and in-vivo rabbit infection model. Histological examination showed that AmB MOP treatment improved the epithelial and stromal differentiation of corneal membrane. AmB containing MOPs can be developed as minimally invasive corneal delivery device for effective treatment of fungal keratitis.


Pancoast's syndrome in a patient with B-cell lymphoma diagnosed and confirmed with immunoglobulin gene rearrangement.
Pancoast's syndrome due to malignant lymphoma is extremely rare. A case of diffuse large B-cell lymphoma presenting as Pancoast's syndrome is described. A 66-year-old man complained of pain and weakness of the right arm, and CXR revealed a right apical lung tumour. Histological findings were consistent with it being a diffuse large cell type lymphoma and Southern blot analysis revealed clonal rearrangement of the immunoglobulin heavy-chain JH. Thus, the tumour in this patient was diagnosed to be diffuse large B-cell lymphoma. Malignant lymphoma is an extremely rare cause of Pancoast's syndrome and only five cases have been described. This is the first reported case of Pancoast's syndrome caused by B-cell lymphoma, which was accurately diagnosed by analysis of gene rearrangement.


Analysis of alcohol ethoxylates and alkylamine ethoxylates in agricultural soils using pressurised liquid extraction and liquid chromatography-mass spectrometry.
Nonionic surfactants e.g. alcohol ethoxylates (AEOs) and alkylamine ethoxylates (ANEOs) are commonly utilised as adjuvants in pesticide formulations to enhance their effectiveness. In this study, analytical methods for AEO and ANEO determination in soil samples using pressurised liquid extraction (PLE) were developed and used in connection with LC-MS. The recovery of the method, which was highly dependent on the soil properties, varied in the range 47-106% for AEO and 27-109% for ANEO. Detection limits (LOD) were 7-13 microg kg(-1) for AEO and 24-43 microg kg(-1) for ANEO. The developed method has been applied to determine AEOs and ANEOs in surface soil samples from fields sprayed with glyphosate herbicides. Tallowalkylamine ethoxylates (an ANEO) were detected in the soil before and after pesticide application, with increasing concentrations after treatment. The highest concentration in the soil samples was observed for the ANEO homologues with the longest ethoxy chains; in the clay soil the concentration decreased with the length of the ethoxy chain. ANEOs added to pesticide formulations as a technical mixture will, as demonstrated in this study, behave as individual homologues, which is reflected in their behaviour in the environment.


Turning grey is not a black-and-white experience: A phenomenological study on the lived experience of old age among Dutch Franciscan friars.
The lack of constructive cultural narratives of old age impedes older people from giving meaning to any difficult circumstances related to aging in which they might find themselves. In this study, we attempted to shed a different light on experiences of meaning in older age to contribute to sources for constructive counter narratives by gaining insight into (the experience of) meaning in old age of Dutch Franciscan friars. The research was a phenomenological in-depth interview study among twelve friars (mean age 80.6 years) following a reflective lifeworld design. The three main themes that emerged from the analysis were (i) 'brotherhood', illustrating a strong, axiomatic sense of connectedness, (ii) 'finitude', illustrating individual and relational confrontations with daily and existential finitude, and (iii) 'dynamic', illustrating opportunities for new possibilities, personal growth and being able to be receptive of the 'good' in daily life. Our findings showed that aging is a multidimensional process that is not exclusively characterized by decline and loss, but also offers substantial opportunities to experience (new) meaning. Occasionally, meaning seemed to arise as a result of (physical) decline. Our results illustrated that under circumstances of connectedness and togetherness, frailty and dependency do not necessarily form a threat to one's autonomy. Connectedness also showed itself to be a source for authenticity, which reinforced the Franciscans as autonomous moral agents.


Kidney Considerations in Pediatric Obesity.
Chronic kidney disease (CKD) is a common condition and a major cause of morbidity and mortality in adults, but children and adolescents are also at risk for early kidney injury and development of CKD. Obesity contributes both directly and indirectly to the development of CKD. The purpose of this review is to describe obesity-related kidney disease (ORKD) and diabetic kidney disease (DKD) and their impact in the pediatric population. Although obesity-related CKD in childhood and adolescence is uncommon, nascent kidney damage may magnify the lifetime risk of CKD. Glomerular hyperfiltration is an early phenotype of both ORKD and DKD and typically manifests prior to albuminuria and progressive decline in GFR. Novel treatments for obesity and type 2 diabetes exerting protective effects on the kidneys are being investigated for use in the pediatric population. It is important to understand the impact of obesity on the kidneys more fully in the pediatric population to help detect injury earlier and intervene prior to the onset of irreversible progression of disease and to guide future research in this area.


Electromyographic and mechanical characteristics of human skeletal muscle during fatigue under voluntary and reflex conditions.
Effects of fatigue produced by a maintained 50% isometric loading on electromyographic (EMG) and mechanical characteristics of voluntary and reflex contractions of human skeletal muscles were studied in 14 males. A continuous isometric loading of the knee extensors caused significant (P less than 0.001) increase in integrated EMG (IEMG) and decrease (P less than 0.001) in mean power frequency (MPF) of the EMG spectrum. The decrease in MPF was related (P less than 0.05) to percentage fast twitch (FT) fibre area of the vastus lateralis muscle. In reflexly induced contractions no changes were observed during fatigue in reflex latency (LAT) but electromechanical delay (EMD) increased significantly (P less than 0.01). The decrease in voluntary MPF and increase in reflex EMD were interrelated (P less than 0.05). Fatigue loading increased (P less than 0.05) the peak-to-peak amplitude of EMG of the reflex contraction but decreased (P less than 0.01) the corresponding force amplitude. The increase (P less than 0.01) in this reflex EMG/force ratio was related (P less than 0.05) to the corresponding increase observed in IEMG/force ratio of the voluntary contraction. The present findings support the differential fatiguing properties of fast twitch and slow twitch muscle fibres. In addition the fatigue effects on reflexly induced contractions show that fatigue took place primarily in the contractile processes and that muscle spindle sensitivity was increased during fatigue loading.


The structural basis of estrogen receptor/coactivator recognition and the antagonism of this interaction by tamoxifen.
Ligand-dependent activation of transcription by nuclear receptors (NRs) is mediated by interactions with coactivators. Receptor agonists promote coactivator binding, and antagonists block coactivator binding. Here we report the crystal structure of the human estrogen receptor alpha (hER alpha) ligand-binding domain (LBD) bound to both the agonist diethylstilbestrol (DES) and a peptide derived from the NR box II region of the coactivator GRIP1 and the crystal structure of the hER alpha LBD bound to the selective antagonist 4-hydroxytamoxifen (OHT). In the DES-LBD-peptide complex, the peptide binds as a short alpha helix to a hydrophobic groove on the surface of the LBD. In the OHT-LBD complex, helix 12 occludes the coactivator recognition groove by mimicking the interactions of the NR box peptide with the LBD. These structures reveal the two distinct mechanisms by which structural features of OHT promote this "autoinhibitory" helix 12 conformation.


GPX5 orthologs of the mouse epididymis-restricted and sperm-bound selenium-independent glutathione peroxidase are not expressed with the same quantitative and spatial characteristics in large domestic animals.
We report here on the cloning of cDNAs coding bovine and equine orthologs of mouse epididymis-restricted and sperm-bound glutathione peroxidase 5 (GPX5), a selenium-independent member of the multigenic GPX family in mammals. The complete sequence of bovine GPX5 as well as a partial sequence of the equine GPX5 were characterized, conceptually translated and aligned with other known mammalian GPX5 proteins. Using Northern blotting assays, we show that the level of expression of GPX5 is high in bovine but low in equine and that in both species the regionalization of GPX5 expression in epididymis is not totally identical to what was reported for rodent mouse GPX5. An antibody was produced against GPX5 and used in Western blot assays as well as in immunohistochemistry assays on bovine epididymis sections. It shows that the protein is essentially present in the cytoplasmic compartment of the caput segment 2 epithelium of the bovine epididymis. Unlike in the mouse model, bovine GPX5 seems to be poorly secreted and does not seem to be present on cauda epididymal spermatozoa.


Long-term elevations of dietary sodium produce parallel increases in the renal excretion of urodilatin and sodium.
The effects of dietary sodium intake on the renal excretion of urodilatin and of sodium were examined in six healthy male subjects. The 24-day study period was divided into three phases of 8 days each. Subjects ingested 2.8 mequiv sodium (kg body weight)-1 day-1 during the first phase, 5.6 mequiv (kg body weight)-1 day-1 during the second phase, and 8.4 mequiv (kg body weight)-1 day-1 during the third phase. The excretion of both sodium (P < 0.002) and urodilatin (P < 0.006) increased in response to the increasing dietary sodium, while urine flow did not change. Urinary urodilatin excretion correlated closely with renal sodium excretion (P < 0.001). Serum aldosterone levels (P < 0.01) as well as serum renin levels (P < 0.05) significantly decreased with increasing sodium intake. Plasma [Arg]vasopressin levels increased significantly (P < 0.05). Plasma atrial natriuretic factor and cGMP levels as well as urinary cGMP excretion rates were unaltered by the changes in sodium intake. We conclude from these results that the renal natriuretic peptide, urodilatin, but not the main cardiac member of the natriuretic peptide family may be involved in the regulation of day-to-day sodium balance.


Functional MRI of the motor cortex using a conventional gradient system: comparison of FLASH and EPI techniques.
Gradient echo (GE) and echo planar imaging (EPI) techniques are two different approaches to functional MRI (fMRI). In contrast to GE sequences, the ultra short EPI technique facilitates fMRI experiments with high spatial and temporal resolution or mapping of the whole brain. Although it has become the method of choice for fMRI, EPI is generally restricted to modern scanners with a strong gradient system. The aim of our study was to evaluate the applicability of EPI for fMRI of the motor cortex using a 1.5 T scanner with a conventional gradient system of 10 mT/m (rise time: 1 ms). Therefore, EPI was compared with a well-established high-resolution fast low-angle shot (FLASH) technique (matrix size 1282). The FLASH technique was applied additionally with a 64(2) matrix size to exclude influences caused by different spatial resolution, because the EPI sequence was restricted to a 64(2) matrix size. A total of 35 healthy volunteers were included in this study. The task consisted of clenching and spreading of the right hand. FLASH and EPI techniques were compared regarding geometric distortions as well as qualitative and quantitative fMRI criteria: Mean signal increase between activation and rest and the area of activation were measured within the contralateral, ipsilateral, and supplementary motor cortex. The quality of subtraction images between activation and rest, as well as the quality of z-maps and time course within activated regions of interest, was evaluated visually. EPI revealed significant distortions of the anterior and posterior brain margins; lateral distortions (relevant for the motor cortex) could be neglected in most cases. The mean signal increase was significantly higher using FLASH 1282 compared to FLASH 64(2) and EPI 64(2), whereas the activated areas proved to be smaller in FLASH 1282 functional images. Both results can be explained by well-documented partial volume effects, caused by different voxel size. Similar quality of the subtraction images and of the time courses in different regions of interest were found for all techniques under investigation, but slightly reduced quality of z-map in FLASH 1282. Within the limits of reproducibility and measurement accuracy, the location of contralateral activation was similar using FLASH and EPI sequences. In conclusion, EPI proved to be a reliable technique for fMRI of the motor cortex, even on an MR scanner with a conventional gradient system.


Fluoride accumulation in soil and vegetation in the vicinity of brick fields.
Fluoride in the soil and vegetation in the vicinity of brick field in the suburb of Lucknow, India was estimated. The water soluble fluoride (1:1) in the surface soil ranged from 0.59 ppm to 2.74 ppm where as CaCl(2) extractable fluoride ranged from 0.69 ppm to 3.18 ppm. The mean total fluoride concentration in surface soil varied from 322 microg g(-1) to 456 microg g(-1). The local vegetations grown in the area found to accumulate air borne fluoride from the brick field. The fluoride accumulation in the vegetation followed the order Mentha arvensis > Spinacea oleracea > Luffa cylindrical.


The cervical factor in patients with ovulatory infertility.
Thirty patients with ovulatory infertility had two consecutive postcoital tests. Couples with inconclusive or abnormal results had in vitro sperm penetration tests, using donor mucus and donor sperm. The quality of the cervical mucus, the concentration of plasma oestradiol and luteinising hormone and the result of the post-coital test were assessed each day. After two consecutive cycles, the postcoital test was normal in 84 per cent, inconclusive in 12 per cent and abnormal in 4 per cent of the women. The in vitro cross reaction test showed that two couples had definite abnormality in the sperm-cervical mucus interaction and one couple were having inadequate coitus. Normal post coital tests should not be expected with an Insler cervical mucus score of less than 8. Normal postcoital tests were found between days -2 and +1 with respect to the luteinising hormone peak. There is a direct relation between the plasma oestradiol concentration and the individual cervical score but the predictability of plasma oestradiol values for a given cervical score is very poor. The plasma oestradiol concentration was significantly different between groups having cervical scores less than 7 and 8-10 or 11-12 (p less than 0.01).