Bear Bile Powder Inhibits Growth of Hepatocellular Carcinoma via Suppressing STAT3 Signaling Pathway in Mice.
To evaluate the inhibitory effect of bear bile powder (BBP) on hepatocellular carcinoma (HCC) growth in vivo and investigate the underlying mechanisms. A HCC xenograft mouse model was developed by producing with huh7 cells. After 5 days following xenograft implantation, ten HCC xenograft mice were given intra-gastric administration with 10 mg/(kg•d) dose of BBP or saline for 3 weeks. Tumor growth in HCC xenograft mice was evaluated by measuring the tumor weight and volume. Cell apoptosis, proliferation or tumor angiogenesis were examined via immunohistochemical (IHC) staining for transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL), proliferating cell nuclear antigen (PCNA) or cluster of differentiation 31 (CD31), respectively. Phosphorylation of signal transducer and activator of transcription 3 (STAT3) were determined by Western blot. The mRNA and protein expressions of Bcl-2, Bax, Cyclin D1 and Cyclin-dependent kinase 4 (CDK4) in HCC tumor tissues were respectively determined by reverse transcription polymerase chain reaction (RT-PCR) and Western blot. The protein expression of vascular endothelial growth factor A (VEGF-A) in tumor tissues was examined by IHC staining. BBP treatment led to a significant decrease on tumor volume and tumor weight in HCC mice (P<0.05) and had no effect on the change of body weight. In addition, BBP profoundly promoted cell apoptosis, inhibited cell proliferation and intratumoral microvessel density in HCC tumor tissues (P<0.05). Moreover, BBP treatment remarkably suppressed the STAT3 phosphorylation and modulated the expression of critical target genes including Bcl-2, Bax, Cyclin D1, CDK4 and VEGF-A in HCC mice. BBP exerts its anti-cancer activities via suppressing STAT3 signaling pathway and affecting multiple intracellular targets.


9-Hydroxyellipticine inhibits telomerase activity in human pancreatic cancer cells.
There is increasing interest in identifying potent inhibitors of telomerase because the enzyme plays a crucial role in the development of cellular immortality and carcinogenesis. We hypothesized that 9-hydroxyellipticine (9-HE), an antitumor alkaloid, would inhibit telomerase activity because the drug has a unique mechanism of inhibiting phosphorylation of mutant p53 protein via inhibition of protein kinases, thereby restoring wild-type p53 function. This study was conducted to examine the effect of 9-HE on telomerase activity in human pancreatic cancer cells with differing p53 gene status. 9-HE treatment at relatively high concentrations resulted in rapid, complete inhibition of telomerase activity, irrespective of the p53 status. We conclude that 9-HE may exert a strong inhibitory effect on telomerase activity possibly through inhibition of protein kinases rather than through restoration of functional wild-type p53.


Polyamine catabolism is concentrated in tumor-associated histiocytes in diffuse large B-cell lymphoma and classic Hodgkin lymphoma.
Polyamines are cationic molecules necessary for cell survival, growth, and replication [1-5]. Polyamines come in a variety of structural forms and are principally regulated by two enzymes, spermine/spermidine acetyltransferase-1 (SAT1) and ornithine decarboxylase-1 (ODC1). SAT1 targets the polyamines spermidine and spermine for degradation via acetylation, while ODC1 is involved in converting the polyamine precursor molecule to more complex polyamines [6-8]. Polyamines and their regulatory enzymes have been implicated in tumor metastasis [9,10] and in crosstalk between oncogenes [11-13] in numerous types of cancer, but their role has never been evaluated in B-cell malignancies. In this study, we examine the expression of SAT1 in diffuse large B-cell lymphoma (DLBCL) and classic Hodgkin lymphoma (HL). We found that SAT1 is expressed in all examined cases of DLBCL (n = 15) and HL (n = 5), though the levels of expression across cases vary. We also note that SAT1 expression appears to be concentrated in tumor-associated histiocytes, rather than tumor cells in both DLBCL and HL. We propose that these findings indicate that the polyamine catabolic enzyme, SAT1, plays an unappreciated role in the pathogenesis of B-cell neoplasms.


Design, synthesis and anticancer activity evaluation of some novel pyrrolo[1,2-a]azepine derivatives.
A novel series of pyrrolo[1,2-a]azepine derivatives 3-7 were synthesized and their structures were confirmed by spectral and elemental analyses. Antitumor activity evaluation of these compounds was carried out against liver (HepG2), breast (MCF7), and colon (HCT116) cancer cell lines using the sulforhodamine-B (SRB) assay method and doxorubicin as reference standard. Compounds 3 and 6 were found to be more potent than doxorubicin against HepG2 cells, with IC50 values of 4, 1.6 and 10.8 nM, respectively. Moreover, compounds 3 and 7 showed broad-spectrum anticancer activity against all the tested cell lines, and their IC50 values were in the nanomolar range (4-44.2 nM and 20.7-45.4 nM, respectively). The 2-benzoylamino derivative of pyrrolo[1,2-a]azepine 5b was the most potent one against MCF7 cells (IC50 of 10.7 nM); however, the 2-(2-chloro-acetylamino)-pyrroloazepine derivative 6 was the most potent against the HCT116 cell line, with an IC50 value of 21.1 nM. The novel compounds were docked into the active site of cyclin-dependent kinase 2 (CDK2) to explore the ability of these compounds to interact with these kinases. All compounds showed a lower binding score energy than the reference ligand.


Mixed multiple system atrophy and progressive supranuclear palsy: a clinical and pathological report of one case.
We report a patient who showed pathological features of both multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) at autopsy. The clinical features included severe cerebellar ataxia, autonomic failure, and rigid-akinetic parkinsonism. The clinical diagnosis was MSA. Pathological examination showed severe neuronal loss with gliosis in the putamen, substantia nigra, inferior olive, and the pontine nucleus, and numerous glial cytoplasmic inclusions. In addition, moderate neuronal loss with gliosis was observed in the globus pallidus and subthalamic nucleus, and neurofibrillary tangles and tufted astrocytes were seen in the basal ganglia and the brain stem. These findings indicate that the patient had both MSA and PSP. Double-labeling immunofluorescence in the brain stem showed alpha-synuclein immunoreactivity localized in the oligodendrocytes and phosphorylated tau immunoreactivity in the neurons and the glia. Co-existence of synucleinopathy and tauopathy is rare.


Complete Genome Sequences of Seven Uropathogenic Escherichia coli Strains Isolated from Postmenopausal Women with Recurrent Urinary Tract Infection.
Uropathogenic Escherichia coli (UPEC) is the most common cause of urinary tract infection (UTI). This disease disproportionately affects women and frequently develops into recurrent UTI (rUTI) in postmenopausal women. Here, we report the complete genome sequences of seven UPEC isolates obtained from the urine of postmenopausal women with rUTI.


Psychiatric liaison consultations of patients without psychiatric illness in a general hospital in Germany: a retrospective analysis.
The aim of the study was to explore the utilization of consultation-liaison psychiatric (CLP) service among nonpsychiatric patients in a general hospital. A retrospective analysis was conducted on all patients seen by the CLP in 2013. In 66 (5.9 %) of these 1112 consultations, no psychiatric diagnosis could be identified. These cases were analyzed by department of referral, assumed psychiatric symptoms, consensus with the symptoms found by the CLP, and recommended procedures. Assumed depressive symptoms, suicidal ideations and "difficult" behavior were the predominant reasons for CLP referrals. As the results suggest, CLP service was mostly "overprovided" because of uncertainty about the working areas of psychiatrists or overestimation of the severity of symptoms. These findings emphasize the importance to develop more precise guidelines for CLP services and that it could be worth striving for a more profound psychiatric training for nonpsychiatric physicians to achieve an optimal treatment for patients.


Phenotyping and Hemodynamic Assessment in Cardiogenic Shock: From Physiology to Clinical Application.
There is growing interest in invasive hemodynamic assessment in cardiogenic shock, primarily due to the widespread adoption of mechanical circulatory support (MCS). Invasive hemodynamic assessment is central to two aspects of cardiogenic shock management: (1) the phenotyping of cardiogenic shock, and (2) the assessment of response to therapy. Phenotyping of cardiogenic shock serves to guide timely therapeutic intervention, and the assessment of hemodynamic response to therapy directs the escalation or de-escalation of therapy, including MCS. This review aims to discuss these two aspects of hemodynamic assessment in cardiogenic shock. Firstly, the physiologic underpinnings of a phenotyping schema, and the implication of the cardiogenic shock phenotype on the MCS strategy in cardiogenic shock will be discussed. Secondly, the concept of cardiac power output and 'effective' oxygen delivery will be discussed in relation to hemodynamic response to therapy in cardiogenic shock.


Robotic Tissue Manipulation and Resection in Spine Surgery.
Spine surgery has evolved from the advent of imaging and navigation guidance, particularly with the rise of robotic surgical assistance. Navigation guidance has demonstrated potential for increased accuracy of transpedicular screw placement and resecting primary and metastatic spinal tumors. Robotic surgery is widely accepted in other surgical fields because laparoscopic techniques applied to robots can increase operator dexterity and improve visualization. Robotic assistance with spinal tumors has enjoyed rising interest owing to the potential for safe and minimally traumatic resection. We discuss available robots used for navigation-guided transpedicular screw placement and state-of-the-art robotic techniques for spinal or paraspinal tumor resection.


[Determination of kinetic parameters lymphocyte populations in cows with chronic lymphocytic leukemia].
We analyzed changes in the number of lymphocytes in the blood of cows with chronic lymphoid leukemia using the Gomperts equation of population dynamics. The parameters of this equation were determined. Coefficients beta and gamma proved to be the most variable. The former reflects the delay and the latter characterizes the maximum rate of growth of the lymphocyte population. According to these parameters, three groups of animals were distinguished with different kinetics of leucosis and different correlations between immuno-hematological indices.


Neurotensin contracts the guinea-pig longitudinal ileal smooth muscle by inducing acetylcholine release.
Neurotensin contracted the isolated longitudinal smooth muscle strip of the guinea-pig ileum, but was only 22% as effective as histamine. Neostigmine (0.1 micrometer) increased the effectiveness of neurotensin 4-fold. Atropine (0.1 micrometer) completely inhibited the contracting effect of neurotensin measured in the presence of neostigmine, whereas hexamethonium (0.1 micrometer) was without effect. It is concluded that in the longitudinal smooth muscle of the guinea-pig ileum, the contracting effect of neurotensin is mediated by the release of acetylcholine from nerve endings in response to a postganglionic stimulation of cholinergic nerve fibers.


Fast pairs: a visual word recognition paradigm for measuring entrenchment, top-down effects, and subjective phenomenology.
When word pairs having a familiar order are sequentially flashed on a computer in their non-familiar order, (code zip), observers have a strong phenomenology of seeing them in familiar order (zip code). Reversal errors remained frequent even when participants obtained perceptual experience of reverse-display items by beginning with a block of longer-duration trials. A forced-choice order-detection procedure reduced but did not eliminate reversal errors, showing that "fast pairs" is a robust perceptual illusion. Even adjective + noun pairs (green skirt) showed reversal errors, and reversal errors increased with the log frequency of the word pair, consistent with a strong role for statistical processing at the level of multi-word units.


Penile cancer: relation of extent of nodal metastasis to survival.
A retrospective review of 199 patients with penile cancer revealed that the extent of inguinal nodal metastasis was related to survival after radical ilioinguinal dissection. Patients with unilateral inguinal nodal involvement had a 56 per cent median 5-year survival rate, whereas those with bilateral inguinal nodal metastasis, extranodal tumor extension or iliac nodal involvement had a 9 per cent median 5-year survival rate.


Role of Ca2+ entry and Ca2+ stores in atypical smooth muscle cell autorhythmicity in the mouse renal pelvis.
Electrically active atypical smooth muscle cells (ASMCs) within the renal pelvis have long been considered to act as pacemaker cells driving pelviureteric peristalsis. We have investigated the role of Ca2+ entry and uptake into and release from internal stores in the generation of Ca2+ transients and spontaneous transient depolarizations (STDs) in ASMCs. The electrical activity and separately visualized changes in intracellular Ca2+ concentration in typical smooth muscle cells (TSMCs), ASMCs and interstitial cells of Cajal-like cells (ICC-LCs) were recorded using intracellular microelectrodes and a fluorescent Ca2+ indicator, fluo-4. In 1 microM nifedipine, high frequency (10-30 min(-1)) Ca2+ transients and STDs were recorded in ASMCs, while ICC-LCs displayed low frequency (1-3 min(-1)) Ca2+ transients. All spontaneous electrical activity and Ca2+ transients were blocked upon removal of Ca2+ from the bathing solution, blockade of Ca2+ store uptake with cyclopiazonic acid (CPA) and with 2-aminoethoxy-diphenylborate (2-APB). STD amplitudes were reduced upon removal of the extracellular Na+ or blockade of IP3 dependent Ca2+ store release with neomycin or U73122. Blockade of ryanodine-sensitive Ca2+ release blocked ICC-LC Ca2+ transients but only reduced Ca2+ transient discharge in ASMCs. STDs in ASMCS were also little affected by DIDS, La3+, Gd3+ or by the replacement of extracellular Cl(-) with isethionate. ASMCs generated Ca2+ transients and cation-selective STDs via mechanisms involving Ca2+ release from IP3-dependent Ca2+ stores, STD stimulation of TSMCs was supported by Ca2+ entry through L type Ca2+ channels and Ca2+ release from ryanodine-sensitive stores.


Continence issues in acute care.
Urinary incontinence affects up to 43 per cent of acute care patients. Toileting is a function of intact bladder, sphincters, and nervous system. Five types of incontinence are stress, urge, reflex, total, and functional. Problems affecting patients in acute care are: 1. Diagnostic studies 2. Treatments--for example, intravenous fluids, hyperalimentation, medications, catheters 3. Bedrest 4. Restraints 5. Pain 6. Iatrogenic conditions 7. Environment Assessment includes a specific history and physical examination, focused on previous episodes of incontinence, functional ability, and cognitive status. Management includes scheduled fluid intake and toileting, manipulation of the environment, and attention to orientation and psychological factors. The treatment of fecal incontinence in the hospital elderly includes: 1. Assessment of incontinence and contributing factors; 2. Bowel regimen and environmental assists for persons with periodic incontinence; 3. Treatment of diarrhea or constipation; and 4. Protection of perineal skin from stool exposure.


Using Blumensaat's line to determine the sagittal alignment of the distal femur.
A coherent measurement approach for sagittal alignment of the distal femur after fracture reduction or distal femur osteotomies is not available. The present study aims to introduce a new method using Blumensaat's line and tangent lines to the femoral cortexes to determine the sagittal alignment of the distal femur. 113 patients who had true lateral knee radiographs were included. All of the radiographs were evaluated by one fellowship-trained knee surgeon and one radiologist using the PACS system. The Blumensaat's line was determined on the true lateral knee radiographs. Then, three long lines were drawn on the distal third of the femoral shaft. The first line is tangent to the anterior cortex of the femur, the second line is along with the anatomical axis of the femur, and the third line is tangent to the posterior cortex of the femur. The angles between Blumensaat's line and these lines were measured. Intraclass Correlation Coefficient (ICC) was used to measure the strength of inter-and intra-rater agreement. The mean angle between the Blumensaat's line and the anatomical axis of the femur was 35.4 ± 3°. The mean angle between the Blumensaat's line and the line tangent to the anterior femoral cortex and the line tangent to the posterior femoral cortex were 34.5 ± 3° and 35.2 ± 3°, respectively. Excellent inter-and intra-rater reliabilities were observed between the measurements (ICC = 0.96 and ICC = 0.98, respectively). The angle between the Blumensaat's line and the line tangent to the posterior femoral cortex was significantly higher in participants aged < 38 years (p = 0.049). No other significant association was found between the angles and demographic characteristics of the patients. The expected mean angles between the Blumensaat's line and the distal femur were 34.3 to 35.4 degrees. This finding could be useful to determine the normal sagittal alignment of the distal femur. II.


Inflammation-related proteins as biomarkers of treatment-related behavioral symptoms: A longitudinal study of breast cancer patients and age-matched controls.
Behavioral symptoms in breast cancer (BC) survivors have been attributed to cancer treatment and resulting inflammation. However, studies linking behavioral symptoms to BC treatment have observed patients only after some treatment. Our prospective study with pre-treatment baseline investigates post-treatment changes in inflammation-related biomarkers and whether those changes correlate with changes in symptoms. Participants were postmenopausal women, newly-diagnosed with stage 0-3 BC before any treatment (n = 173 "patients"), and age-matched women without cancer (n = 77 "controls"), who were assessed on plasma markers [soluble tumor necrosis factor receptor type 2 (sTNF-RII), interleukin (IL)-6, IL-1 receptor antagonist (IL-1RA), C-reactive protein (CRP)]) and symptoms (Physical Functioning, Pain, Attention/concentration, Perceived Cognitive Problems, Fatigue, Sleep Insufficiency, Depression). Participants were assessed again 1 month, 1 year, and 2 years after completing primary treatment or similar interval in controls. Generalized linear mixed models tested 4 treatments (surgery alone or with chemotherapy, radiation, or both) for association with change per marker. Joint models tested change per marker for association with change per symptom. Models considered demographic, socioeconomic, and clinical covariates. False Discovery Rate method controlled risk of error from multiple hypotheses. At one month post-completion of treatment, sTNF-RII and IL-6 were elevated by all BC treatments, as were IL-1RA and CRP after surgery alone (all, p < 0.05). By 1 year, markers' average values returned to baseline. Throughout 2-year follow-up, increase-from-baseline in sTNF-RII, IL-1RA, and IL-6 coincided with worsened Physical Functioning, and increase-from-baseline in sTNF-RII coincided with increased Pain (all, p < 0.01). These biomarker-symptom associations (excepting IL-6) were exclusive to patients. No other symptoms worsened, and baseline Fatigue and Depression improved in all participants. BC treatment, even surgery, is associated with transient elevation in inflammatory markers. In patients post-treatment, increase-from-baseline in sTNF-RII accompanies increased Pain and decreased Physical Functioning, suggesting that sTNF-RII merits development as a clinical biomarker in BC patients.


Aneurysmal bone cyst of the spine: computed tomographic appearance.
Computerized tomography can depict most of the characteristic features of aneurysmal bone cyst of the spine even when the plain film findings are not diagnostic. The computed tomographic appearance is that of a benign expansile soft tissue mass surrounded by a shell of bone, an appearance which is analogous to the typical changes of aneurysmal bone cyst in the extremities. Extension into adjacent bones and soft tissues can be demonstrated and thereby facilitate both preoperative planning and later follow-up for recurrence.


Auditory frequency discrimination in the white rat.
Frequency discrimination was investigated in the albino rat using a modified go/no-go positive reinforcement procedure in which subjects reported frequency increments in an ongoing series of pure tone bursts. Weber ratios (frequency difference limen/frequency) were measured from 5 to 32 kHz at 50 dB sound pressure level. A signal detection analysis of the procedure enabled a direct comparison to be made with the rat's performance in a discrete trial go/no-go task. A mean Weber ratio of 3.06+/-0.44% was measured in the frequency range 5-32 kHz. This indicates that the rat has better frequency discrimination acuity than has previously been thought. The result is discussed in the context of factors affecting performance. Among the factors that were explored we found that long training times and the specific training paradigm played important roles. In comparison to discrete trial go/no-go paradigms, rats performed much better when detecting signals from a repeating background. Frequency discrimination performance decreased linearly for tones less than 50 ms in duration. For longer tone duration performance was unaffected. The means and variability of reaction times for threshold changes of frequency were greater in comparison with supra-threshold frequency changes.


[A new improved medico-statistical document for registration of the therapeutic work and planned prophylactic activity of the stomatologist].
A complete description is presented of the new registration document "Stomatologist's journal", used for planning, registration, analysis and evaluation of the stomatological activity. The main requirements for keeping the journal are interpreted which will facilitate the stomatological personnel in its implementation in the practice. The authors think that the "Stomatologist's journal" could be used as a personal service record of each stomatologist.


Microstructural network alterations of olfactory dysfunction in newly diagnosed Parkinson's disease.
Olfactory dysfunction is a robust and early sign for Parkinson's disease (PD). Previous studies have revealed its association with dementia and related neural changes in PD. Yet, how olfactory dysfunction affects white matter (WM) microstructure in newly diagnosed and untreated PD remains unclear. Here we comprehensively examined WM features using unbiased whole-brain analyses. 88 newly diagnosed PD patients without dementia (70 with hyposmia and 18 without hyposmia) and 33 healthy controls underwent clinical assessment and diffusion tensor imaging (DTI) scanning. Tract-based special statistics (TBSS), graph-theoretic methods and network-based statistics (NBS) were used to compare regional and network-related WM features between groups. TBSS analysis did not show any differences in fractional anisotropy and mean diffusivity between groups. Compared with controls, PD patients without hyposmia showed a significant decrease in global efficiency, whilst PD patients with hyposmia exhibited significantly reduced global and local efficiency and additionally a disrupted connection between the right medial orbitofrontal cortex and left rectus and had poorer frontal-related cognitive functioning. These results demonstrate that hyposmia-related WM changes in early PD only occur at the network level. The confined disconnectivity between the bilateral olfactory circuitry may serve as a biomarker for olfactory dysfunction in early PD.


A model for evaluation of enterprise architecture quality.
Today, most organizations use an enterprise architecture (EA) approach as a tool to increase the power of management on the organization's information technology. Enterprise architecture is a set of processes that helps an organization to translate its vision into an effective change in the organization's scope by providing a clear understanding of its current state. The purpose of this research is to identify EA quality attributes and its evaluation indicators in the organization. This study was conducted by using mixed method, including qualitative and quantitative parts. In the qualitative section, a variety of EA evaluation indicators were identified by a systematic literature review (SLR) approach, then in the quantitative section the survey data were collected by a questionnaire prepared based on the qualitative part and then exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were performed. This research presents an EA evaluation model that has seven main quality attributes including alignment and integrity, quality of EA products and services, security, maintainability and portability, reliability, reusability and scalability, and 30 indicators that address all aspects of enterprise architecture. Through this model, organizations can evaluate the quality of implemented EA or AS-IS status of EA and take steps to improve it.


Distribution and Release of Mercury Regulated by the Decomposition of a Pioneer Habitat-Adapted Plant in the Water-Level-Fluctuating Zone of the Three Gorges Reservoir.
Pioneer habitat-adapted bermudagrass is prevalent in the water-level-fluctuating zone of the Three Gorges Reservoir area. This study was performed to explore the response characteristics of dissolved organic matter (DOM) qualities to bermudagrass decomposition and their regulation in the distribution and release of mercury (Hg) and methylmercury (MeHg) in the soil-water system. Compared to the control, the bermudagrass decomposition resulted in a great increase in the protein-like components in the water in the initial stages (p < 0.01), but it also greatly reduced the humification degree of water DOM (p < 0.01). However, it accelerated the consumption of protein-like components, the humification rate, and the synthesis of humic-like DOM in the water over time. This changing pattern of the DOM qualities resulted in an initial elevation and a subsequent great decrease in the dissolved Hg and MeHg concentrations in the pore water, which ultimately reduced their release levels into the overlying water by 26.50% and 54.42%, respectively, compared to the control. Our results indicate the potential inhibitory effects of short-term bermudagrass decomposition caused by flooding and how decomposition affects the release of total Hg and MeHg by shaping the DOM qualities, and they have implications for similar aquatic systems in which herbaceous plants are frequently decomposed after submergence.


Vitamin D Levels in Patients With Type 2 Diabetes Mellitus.
Vitamin D may influence many diseases, including type 2 diabetes mellitus. We studied serum levels of 25-hydroxyvitamin D (25(OH)D) and associated characteristics in type 2 diabetic outpatients with pharmacologic treatment attended in internal medicine offices in a first-level hospital from Extremadura (Southern Spain). We included a total of 103 patients. Seventy-two patients (69.9%) had serum levels of 25(OH)D lower than 20 ng/mL. There was inverse correlation between serum levels of 25(OH)D and glycosylated hemoglobin (r = -0.74, P = 0.01). In 78 patients without insulin therapy, we found inverse correlation between serum levels of 25(OH)D and fasting serum insulin (r = -0.82, P = 0.001) and Homeostasis Model Assessment-Insulin Resistance (r = -0.51, P < 0.001). Vitamin D deficiency is common in type 2 diabetic patients. There are inverse correlations between vitamin D and metabolic control and insulin resistance.


Morphological evaluation of Day 8 embryos developed during induced aluteal cycles in the mare.
A novel in vivo model utilizing serial administrations of PGF2α to induce aluteal cycles in the mare was used to evaluate the effects of progesterone-deprivation on the morphology of in vivo preimplantation embryos. We hypothesized that equine embryos produced during induced aluteal cycles (AL) would be developmentally affected, characterized by earlier embryo stage at collection, smaller embryo diameter, and lower quality grade, compared with those collected on the same day post-ovulation from control cycles during diestrus (high progesterone; > 4 ng/mL). Seven cyclic mares with a median age of 6.5 years (range 3-16) were utilized in a crossover design. Mares in estrus were artificially inseminated to a fertile stallion and randomly assigned to control or AL groups. Mares received either saline solution (control mares) or PGF2α (AL mares), twice daily on days 0, 1, and 2 and once daily on days 3 and 4. Serial blood samples were collected daily during estrus and until the day of embryo collection 8 days after ovulation. Mares were monitored until they returned to estrus, and artificially inseminated. Mares were switched to the opposite treatment group only after a successful embryo collection occurred during the previous cycle. Only cycles that produced embryos were used for analyses. No significant rise in progesterone was observed in the AL group with mean concentrations of plasma progesterone remaining <1.0 ng/mL from ovulation until embryo collection on Day 8. This is in sharp contrast to the control (luteal) cycle where a post-ovulatory rise in plasma progesterone was observed. The mean daily concentrations of plasma progesterone were significantly higher in control vs. AL group beginning at Day 3 and remained so until Day 8. The mean (±SEM) embryo diameter of AL embryos was 171 ± 5 μm compared to 756 ± 99 μm for control embryos. The majority of the Day 8 AL embryos were classified as morulas (3/9) or early blastocysts (5/9) with only 2 embryos of quality grade 1 compared to the Day 8 control embryos that were mostly expanded blastocysts (6/7) with 5 of 6 being of quality grade 1. This study shows that serial administrations of PGF2α were able to prevent significant rises in plasma progesterone, thus inducing aluteal cycles characterized by a progesterone-deprived environment for developing embryos. Embryos collected from induced aluteal cycles were adversely affected as demonstrated by a lower quality grade, smaller diameter and earlier embryo stage at collection when compared to control embryos.


Effects of altered thyroid states and undernutrition on the calbindin-D28K (calcium-binding protein) content of the hippocampal formation in the developing rat.
A quantitative study of calbindin-D28K (calcium-binding protein) was carried out on the developing hippocampal formation in normal, hypothyroid, hyperthyroid, and underfed rats. In normal animals, the calbindin-D28K content increased after birth in agreement with the distribution of the protein previously reported by immunocytochemistry. Calbindin-D28K was strikingly spared, compared to the other proteins, from the effects of hypothyroidism. On the contrary, the calbindin-D28K:protein ratio was transiently reduced by hyperthyroidism. Corrective doses of thyroxine to hypothyroid rats increased the calbindin-D28K content whatever the period of the hormonal treatment, but they also had a marked effect on the hippocampal weight and the protein content, especially when the hormone was given on days 2-3. With this latter replacement therapy schedule, the calbindin-D28K:protein ratio dropped from the high value of the hypothyroid animal to normal. Taken together, the results obtained in hypothyroidism, hyperthyroidism and replacement therapy are consistent with a pronounced action of thyroid hormone on hippocampal structures other than those containing calbindin-D28K. Undernutrition, which, like hypo- or hyperthyroidism, also markedly impairs hippocampal growth, affected the calbindin-D28K content per hippocampus but not the calbindin-D28K:protein ratio. This emphasizes the unique influence of thyroid hormone on brain development. The relative preservation of calbindin-D28K in the hippocampal formation of animals lacking thyroid hormone suggests that calbindin-D28K function may be crucial in this brain region.


Presence and regulation of ATP:citrate lyase from the citric acid producing fungus Aspergillus niger.
ATP:citrate lyase (EC 126.96.36.199) has been identified in cell-free extracts from the filamentous fungus Aspergillus niger. The enzyme was located in the cytosol. It exhibits an activity at least ten times that of acetate-CoA-kinase (EC 22.214.171.124) during growth on carbohydrates as carbon sources, and is thus considered responsible for acetyl-CoA formation under these conditions. It is formed constitutively and its biosynthesis does not appear to be controlled by changes in the nitrogen or carbon source or type. ATP:citrate-lyase appears to be very labile during conventional purification procedures; a method involving fast protein liquid anion exchange chromatography was thus developed in order to obtain enzyme preparations sufficiently free of enzymes which could interfere with kinetic investigations. This preparation displays commonly known characteristics of ATP:citrate lyase with respect to substrate affinities and cofactor requirements, with the exception that the affinity for citrate is rather low (2.5 mM). No activator was found. The enzyme is inhibited by nucleoside diphosphates, nucleoside monophosphates and palmitoyl-CoA. Regulation of ATP:citrate lyase be the energy charge of the cytosol in relation to lipid or citric acid accumulation is discussed in view of these findings.


Active for a day: predictors of relapse among previously active mass event participants.
To promote maintenance of sufficient physical activity (PA), better understanding of factors associated with behavioral relapse is needed. To identify PA relapsers and predictors of this state in a large community sample of women who participated in 2 mass 10-km events in Ireland. Relapsers to 'low active' were identified at 3-month follow-up, and factors associated with relapse investigated. 11% of the sample decreased their participation by at least 60 minutes of moderate-intensity PA per week and regressed to 'insufficiently active.' Adjusted analysis indicated relapse was associated with walking the event (OR = 1.40; 95% CI = 1.05-1.85) and not achieving tertiary education (OR = 1.49; 95% CI = 1.18-1.88). Normal-range BMI, training continuously, urban residence, and increases in self efficacy and positive perceptions of the physical environment were related to lower incidence of relapse. Education, living in an urban area, BMI, walking the event, training, and self efficacy are all associated with relapse and while mass events are a useful motivator for PA, strategies are required following events to maintain participation levels and generate a lasting public health impact.


The association of pretreatment low skeletal muscle mass with chemotherapy dose-limiting toxicity in patients with head and neck cancer undergoing primary chemoradiotherapy with high-dose cisplatin.
Low skeletal muscle mass (SMM) is an adverse prognostic factor for chemotherapy dose-limiting toxicity (CDLT). In patients with locally advanced head and neck squamous cell carcinoma (HNSCC) undergoing chemoradiotherapy (CRT), low SMM is a predictor for CDLT. We aimed to validate these findings. Consecutive LA-HNSCC patients treated with primary CRT with high-dose cisplatin were retrospectively included. SMM was measured on pre-treatment CT-imaging. A cumulative cisplatin dose below 200 mg/m2 was defined as CDLT. One hundred and fifty three patients were included; 37 (24.2%) experienced CDLT, and 84 had low SMM (54.9%). Patients with low SMM experienced more CDLT than patients with normal SMM (35.7% vs. 10.1%, p < 0.01). Low SMM (OR 3.99 [95% CI 1.56-10.23], p = 0.01) and an eGFR of 60-70 ml/min (OR 5.40 [95% CI 1.57-18.65], p < 0.01) were predictors for CDLT. Pre-treatment low SMM is associated with CDLT in LA-HNSCC patients treated with primary CRT. Routine SMM assessment may allow for CDLT risk assessment and treatment optimization.


Ankyloblepharon-ectodermal dysplasia-clefting syndrome misdiagnosed as epidermolysis bullosa and congenital ichthyosiform erythroderma: Case report and review of published work.
A Chinese female infant presented with ectodermal dysplasia, cleft palate and severe skin erosions at birth. Although all the typical clinical features of ankyloblepharon-ectodermal dysplasia-clefting (AEC) syndrome were present, the ankyloblepharon was not very marked. We misdiagnosed epidermolysis bullosa and congenital ichthyosiform erythroderma at first and confirmed the diagnosis of AEC syndrome only when she presented with the typical clinical manifestation of recurrent infected scalp erosions at 1 year of age. Mutation analysis of exon 13 of the p63 gene revealed a missense mutation Ile482Thr (c.1445T>C) in the sterile alpha motive domain. In this work we review the clinical features, differential diagnosis and prognosis in AEC syndrome.


Research on the Tournament Incentive Mechanism of the Safety Behavior for Construction Workers: Considering Multiple Heterogeneity.
The unsafe behavior of construction workers is one of the most important and direct causes of safety accidents. Managers usually develop effective incentives aimed at regulating worker safety behavior. Due to the large number of workers in construction projects, there are multiple differences in fairness preference, risk preference and ability level, which will lead to the complex effect of the traditional mechanism to regulate workers' safety behavior. In order to improve the effectiveness of incentive measures for worker safety behavior, this paper takes into account the multiple differences of individual workers' fairness preference, risk preference and ability level, based on the tournament mechanism to construct a competition incentive model. By designing a tournament reward and salary distribution for heterogeneous workers, the occurrence of unsafe behaviors can be reduced. The study found that in terms of the optimal level of safety investment, workers with risk aversion attitude generally invest higher than that of workers with risk preference, no matter whether they have a strong fairness preference or not; In terms of the distribution of tournament rewards, workers with a risk aversion attitude and a higher level of fairness preference need to be given higher incentives.


Sulfonamidolactam inhibitors of coagulation factor Xa.
As part of an effort to identify novel backups for previously reported pyrazole-based coagulation Factor Xa inhibitors, the pyrazole 5-carboxamide moiety was replaced by 3-(sulfonylamino)-2-piperidone. This led to the identification of a structurally diverse chemotype that was further optimized to incorporate neutral or weakly basic aryl and heteroaryl P1 groups while maintaining good potency versus Factor Xa. Substitution at the sulfonamide nitrogen provided further improvements in potency and as did introduction of alternate P4 moieties.


Impact of micronutrient deficiency & malnutrition in systemic sclerosis: Cohort study and literature review.
The purpose of our study was to determine the prevalence and risk factors associated with malnutrition, and selenium (Se) and vitamin C (vitC) deficiencies in systemic sclerosis (SSc) patients. We included adult SSc patients fulfilling the 2013 ACR/EULAR criteria from the Toulouse University Hospital cohort who underwent a micronutrient workup (including vitC, Se or thiamine levels) between 2011 and 2016. 82 patients were included, mostly women (76%), with a median age of 60 years. SSc was limited in 76% of the cases, with Scl-70 and centromere antibodies in 32% and 44%, respectively. Median disease duration was 7.4 years. Cardiac involvement was noticed in 19% and gastrointestinal tract in and 95%; 9% had pulmonary artery hypertension (PAH) and 63% had interstitial lung disease. Overt malnutrition was present in 14 (17%) patients. Micronutrient deficiencies included Se (35%), vitC (31%) and/or thiamine (6%). Malnourished patients had significantly a higher summed Medsger disease severity scales (7.5 vs. 5, P = .003), lower hemoglobin (10.6 vs. 12.9 g/dL, P < .0001) and vitC levels (3.6 vs. 10.6 mg/L, P = .003). Cardiac involvement was significantly associated with Se deficiency (OR 6.2, IC 95%[1.48-32.70], P = .05). The factors associated with vitC deficiency were malnutrition (OR 8.57, IC 95%[2.16-43.39], P = .003), modified Rodnan skin score ≤ 14 (OR 0.33, IC95[0.11-1], P = .05), PAH (27% in deficient vs. none in non-deficient patients, P = .0006) and esophagitis or Barrett's mucosa (OR 4.05, IC95[1.27-13.54], P = .02). Se testing should be considered as soon as cardiac involvement is suspected. VitC testing should be considered in malnourished SSc patients, especially if skin involvement is extensive.


Guideline Recommendations for Empirical Antimicrobial Therapy: An Appraisal of Research Evidence for Clinical Decision-Making in Ethiopia.
The rapid spread of drug resistance is forcing standard treatment guidelines (STGs) to become more appropriate with due consideration of the evidence on the antimicrobial resistance (AMR) situation in Ethiopia. Therefore, we aimed to assess the local AMR recommendations in the STGs for empirical antibacterial prescriptions for the five common infectious syndromes. We also determined the quality of AMR reviews conducted in the country. We conducted a review of the STGs used in the health centers, general hospitals, and primary hospitals in Ethiopia and assessed the AMR recommendations in STGs for empirical antibacterial prescriptions for community-acquired pneumonia (CAP), urinary tract infection (UTI), tonsillopharyngitis, acute otitis media (AOM), and bacterial dysentery. Next, we performed an overview of AMR reviews published in Ethiopia. We used the MEDLINE/PubMed, Embase, Cochrane Library, and Google Scholar databases to identify AMR reviews. The review characteristics were extracted. We also evaluated the quality of each included AMR review using a measurement tool to assess the systematic review scale (AMSTAR 2). A total of 6 STGs and 12 AMR reviews conducted in the country were included. The choice of empirical antibacterials for similar infectious syndromes (and editions) was comparable across the three levels of the health care system. None of the STGs evaluated included the local AMR recommendations for empirical antibacterial prescriptions for five common infectious syndromes. Of all the AMR reviews included, 75% had low and below methodologic quality, and none had a high-quality score using the AMSTAR 2 tool. Standard treatment guidelines did not consider local AMR recommendations for empirically prescribing antibacterials for common infectious syndromes. The AMR reviews published in the country produced poor methodologic quality evidence for clinical applications. This highlights the need to improve the methodologic quality to provide the best available evidence for clinical decision-making and curb the ongoing AMR in Ethiopia. Retrospectively registered (15/07/2020).


Circadian rhythm of corticosterone secretion in the neonatal rabbit.
Maternal care in the rabbit is restricted to a single 3- to 5-min period of nursing each day. One to three hours prior to the arrival of the mother, pups exhibit anticipatory behavioral arousal and elevation of core body temperature. In rodents, the hypothalamic-pituitary-adrenal axis is quiescent and levels of the adrenal hormone, corticosterone (CORT), are stable and extremely low during the first days of life, which are known collectively as the stress-hyporesponsive period (SHRP). It has been proposed that the rabbit also has an SHRP. However, we decided to examine CORT changes associated with the daily nursing bout, since behavioral arousal, core body temperature, and CORT are elevated prior to the onset of feeding in many other species. We scheduled the nursing bout at 1000 h and analyzed CORT concentration using RIA in pups sampled at various intervals after suckling. CORT levels showed a circadian variation that peaked at the time of the daily nursing bout. After nursing, values steadily decreased to a nadir at 2200 h and then rose again in advance of the next scheduled nursing. The three-fold difference between the highest (1000 h) and the lowest (2200 h) CORT values suggests that either the SHRP does not exist in rabbit pups or else it has properties that differ from those described for rodents. Unlike rodents, rabbit pups show a circadian secretion of CORT synchronized to the scheduled nursing bout.


Resveratrol-Loaded Polymeric Nanoparticles: The Effects of D-α-Tocopheryl Polyethylene Glycol 1000 Succinate (TPGS) on Physicochemical and Biological Properties against Breast Cancer In Vitro and In Vivo.
Resveratrol (RSV), a phytoalexin from grapes and peanuts, has been reported to exhibit antiproliferative effects on various cancer cell lines. In breast cancer, RSV has been demonstrated to exert an antiproliferative effect on both hormone-dependent and hormone-independent breast cancer cell lines. However, RSV is a lipophilic drug, and its therapeutic effect could be improved through nanoencapsulation. Functionalizing polymeric nanoparticles based on polycaprolactone (PCL) with polyethylene glycol 1000 tocopheryl succinate (TPGS) has been reported to prolong drug circulation and reduce drug resistance. However, the effect of TPGS on the physicochemical properties and biological effects of breast cancer cells remains unclear. Therefore, this study aimed to develop RSV-loaded PCL nanoparticles using nanoprecipitation and investigate the effect of TPGS on the nanoparticles' physicochemical characteristics (particle size, zeta potential, encapsulation efficiency, morphology, and release rate) and biological effects on the 4T1 breast cancer cell line (cytotoxicity and cell uptake), in vitro and in vivo. The optimized nanoparticles without TPGS had a size of 138.1 ± 1.8 nm, a polydispersity index (PDI) of 0.182 ± 0.01, a zeta potential of -2.42 ± 0.56 mV, and an encapsulation efficiency of 98.2 ± 0.87%, while nanoparticles with TPGS had a size of 127.5 ± 3.11 nm, PDI of 0.186 ± 0.01, zeta potential of -2.91 ± 0.90 mV, and an encapsulation efficiency of 98.40 ± 0.004%. Scanning electron microscopy revealed spherical nanoparticles with low aggregation tendency. Differential Scanning Calorimetry (DSC) and Fourier Transform Infrared Spectroscopy (FTIR) identified the constituents of the nanoparticles and the presence of drug encapsulation in an amorphous state. In vitro release studies showed that both formulations followed the same dissolution profiles, with no statistical differences. In cytotoxicity tests, IC50 values of 0.12 µM, 0.73 µM, and 4.06 µM were found for the formulation without TPGS, with TPGS, and pure drug, respectively, indicating the potentiation of the cytotoxic effect of resveratrol when encapsulated. Flow cytometry and confocal microscopy tests indicated excellent cellular uptake dependent on the concentration of nanoparticles, with a significant difference between the two formulations, suggesting that TPGS may pose a problem in the endocytosis of nanoparticles. The in vivo study evaluating the antitumor activity of the nanoparticles confirmed the data obtained in the in vitro tests, demonstrating that the nanoparticle without TPGS significantly reduced tumor volume, tumor mass, maintained body weight, and improved survival in mice. Moreover, the biochemical evaluation evidenced possible hepatotoxicity for formulation with TPGS.


Longitudinal observation on reproductive and lactation performances of smallholder crossbred dairy cattle in Fitche, Oromia region, central Ethiopia.
A two-year longitudinal study was conducted to assess the reproductive and lactation performances of smallholder crossbred dairy cattle in Fitche, central Ethiopia. Twenty-four smallholder dairy farms were monitored and data on reproductive, breeding, lactation and management aspects of crossbred dairy cows (n=69) were collected and analysed. Moreover, milk samples were collected and analysed for progesterone. The overall Least-squares means for calving interval (CI), calving to conception interval (CCI) and first observed oestrus after calving were 516, 253 and 141 days, respectively. Suckling significantly prolonged these intervals. The mean first onset of luteal activity (OLA) after calving was 52 days, while 67.4% n=43) had a delayed (>55 days) return to cyclicity after calving. Suckling and parity number significantly (p < 0.05) influenced the OLA. The mean lactation length was 54.4 weeks. The overall daily mean milk yield for the first 43 weeks of lactation after calving was 11.7 L/day. The estimated daily milk yield increased slowly and reached peak (13.8 L/day) around the 11th week post partum and declined gradually and steadily. Suckling status, season of calving and parity number significantly influenced the estimated daily milk yield. In conclusion, the present study indicated that the smallholder crossbred dairy cows in the study area had prolonged intervals to first oestrus after calving, to conception and to the next calving, and thus their reproductive performance is unsatisfactory. Delayed first onset of luteal activity (postpartum anoestrus) contributed to these extended intervals. Further detailed investigation is suggested to examine the effects of other relevant factors on the reproductive and lactation performances of smallholder crossbred dairy cows for appropriate intervention.


Guanosine triphosphate-binding proteins on the plasmalemma of spinach leaf cells.
The molecular mechanism of light perception through phytochrome is not well understood. This red-light photosensor has been implicated in various physiological processes, including the photoinduction of flowering. A few recent studies have shown that phytochrome initiates signal transduction chains via guanosine triphosphate (GTP)-binding proteins (G-proteins). We show here by different approaches that G-proteins exist in spinach (Spinacia oleracea L. cv. Nobel). Binding of GTP on the plasmalemma has been partially characterized and its possible regulation by red light examined by in-vitro assays. These experiments indicate a clear regulation of GTP binding by red light and also by Mastoparan. At least three G-proteins or protein subunits were found to be associated with the plasmalemma of leaf cells. The use of an antibody raised against an animal Gβ subunit confirmed the presence of heterotrimeric G-proteins. Separation of a crude membrane extract by free-flow electrophoresis also showed that some G-proteins could exist on the tonoplast.


Analysis of creams. V. Application of thin layer chromatography. Part II.
A standard TLC procedure was tested for its applicability in the qualitative analysis of several creams. It was found that in creams of known composition the presence of almost all of the active cream components as well as the excipients can be confirmed. An additional eluent, spray reagent, or a liquid extraction clean-up step sometimes appeared to be necessary. If the cream base composition is not known, a 'fingerprint' of the various types of excipients is obtained with the described procedure.


Increase in androgen:estrogen ratio specifically during low-dose follicle-stimulating hormone therapy for polycystic ovary syndrome.
To compare changes in serum androgens in women with polycystic ovary syndrome (PCOS) during ovulation induction with low-dose versus conventional urofollitropin. Prospective case-control study. Tertiary-care reproductive medicine center. Thirty-three women with PCOS who failed to conceive with clomiphene citrate therapy. Urofollitropin (low-dose, 75 IU; conventional dose, 150 IU) was administered IM daily. Therapy was monitored by serum E2 and vaginal sonography. Hormone determinations were performed by immunoassay. Serum E2, androstenedione (A), T, and LH levels. On the day of hCG administration, patients treated with low-dose therapy exhibited significantly higher ratios of A to E2 (3.5 +/- 0.5 versus 2.2 +/- 0.3 [mean +/- SEM]) and T to E2 (1.5 +/- 0.3 versus 1.0 +/- 0.1) compared with conventional urofollitropin therapy. The number of follicles > or = 16 mm in diameter was significantly lower with low-dose therapy (2.7 +/- 0.6 versus 5.4 +/- 0.4). Although low-dose therapy was associated with a reduction in the number of recruited follicles, the increase in androgen to E2 associated with this therapy may adversely affect oocyte quality and may explain the relatively high miscarriage rate reported in PCOS patients with this therapy.


Laboratory evidence that dinotefuran, pyriproxyfen and permethrin combination abrogates Leishmania infantum transmissibility by sick dogs.
Dogs are reservoir hosts of leishmaniasis caused by Leishmania infantum and transmitted by phlebotomine vectors. The effect of dinotefuran, pyriproxyfen and permethrin spot-on solution (Vectra®3D, Ceva Santé Animale, Libourne, France) on Leishmania transmissibility by naturally infected dogs via reared Phlebotomus perniciosus, was assessed. Dogs affected by leishmaniasis were submitted to xenodiagnosis and 6 infecting >10% of insects were treated topically on day 0. Antifeeding, insecticidal and anti-transmissibility effects were evaluated through xenodiagnoses performed on days 1, 7 and 28, using individual pre-treatment parameters as control. Feeding and mortality rates were assessed at 24 h, whereas promastigote infection, maturation and burden were assessed up to 96 h post blood meal (potentially infectious rate). On day 1, the anti-feeding efficacy was >95% in 4 dogs, insecticidal efficacy 100% in 4 dogs, and anti-transmissibility effect 100% in 6 dogs. Efficacy rates recorded on day 7 were very similar to day 1. On day 28, anti-feeding and insecticidal efficacy values were much broader, ranging 32.6-100% and 7.7-94.4%, respectively. Potentially infectious insects were recorded from two dogs, with sharp decrease in transmissibility rate as compared with pre-treatment condition. Altogether, Vectra®3D abrogated by >98% the potential Leishmania transmissibility by the examined pool of infected dogs over 1 month.


Forecasting water quality parameters using artificial neural network for irrigation purposes.
This study was aimed at analyzing the water quality of Ele River Nnewi, Anambra State for irrigation purposes with a view to predicting a one-year water quality index using Artificial Neural Network (ANN). Water pollution has posed a major problem and identifying the points of pollution in the River system is a very difficult task. To overcome this task, the need to determine the pollution level arose by modeling and predicting four water quality parameters at four (4) different locations using the Artificial Neural Network. These parameters include the pH, Total Dissolved Solids (TDS), Electrical Conductivity (EC), and Sodium (Na), respectively. The water quality results showed that the pH values which ranges from 6.01 to 6.87 were within the FAO standard in all the points for both rainy and dry seasons, whereas the TDS (mg/l), EC (dS/m) and Na (mg/l) parametric values range from 2001 to 2506, 3.01 to 5.76, and 40.42 to 73.45 respectively, were above the FAO standard from point 1 to point 3 and falls within the FAO standard at point 4 with values ranging from 1003 to 1994, 2.01 to 2.78 and 31.24 to 39.44, respectively. However, during the dry season, the TDS, EC, and Na values range from 2002 to 2742, 3.04 to 5.82 and 40.14 to 88.45 respectively, were all above the FAO standard. Generally, the artificial neural network modeled the actual water quality data set very well with good prediction. The training model performance evaluation shows that the R2 values ranges from 0.981 to 0.990, 0.981 to 0.988, 0.981 to 0.989 and 0981 to 0.989, for pH, TDS, EC, and Na. The testing model performance shows that the R2 value ranges from 0.952 to 0.967, 0.953 to 0.970, 0.951 to 0.967and 0.953 to 0.968, for pH, TDS, EC and Na while the forecast performance evaluation shows that the R2 values ranges from 0.945 to 0.968, 0.946 to 0.968, 0.944 to 0.967 and 0.949 to 0.965 for pH, TDS, EC and Na respectively. It was also observed that the Root Mean Squared Error (RMSE) ranges from 0.022 to 0.088, 0.012 to 0.087, 0.015 to 0.085 and 0.014 to 0.084 for pH, TDS, EC and Na, respectively. Information from this study will serve as a guide to researchers on the water quality index for irrigation purposes. Also, it will guide the government and agencies on policy, management and decision-making on water resources.


Long-term follow-up of the clinical relevance of short outer dynein arms in human nasal cilia.
Clinical significance of short outer dynein arms was examined in a long-term follow-up study of 76 patients with various respiratory symptoms. Clinical evaluations, nasal mucociliary transport rate (NMTR) measurement and transmission electron microscopy were performed. Follow-up examinations took place 5-11 years later. In the initial examination four patients and on follow-up seven patients were found to have short outer dynein arms in their nasal mucosal biopsies. Short dynein arms were associated with a slow NMTR, poorly coordinated ciliary beat direction, and clinical symptoms of perennial rhinitis and recurrent sinusitis. Short dynein arms were found to be a significant histologic finding and probably represent a variant of primary ciliary dyskinesia. In some cases short outer dynein arms may be a reversible finding with improving clinical symptoms. It is obvious that at least part of dynein defects are acquired.


Hyperuricemia as a risk factor on cardiovascular events in Taiwan: The Chin-Shan Community Cardiovascular Cohort Study.
Little is known about uric acid role for cardiovascular events in the Asian-Pacific countries with relatively low coronary heart disease (CHD) but high stroke events. Also, there is scanty evidence for repeated measures of uric acid levels among population. We examined associations of basic and repeated measures of uric acid level with CHD and stroke events in one Taiwanese adult community prospectively. Cox proportional hazards models, treating uric acid as baseline and time-dependent covariates, were used to assess the 11-year risk of CHD and stroke events. Among 3602 adult subjects older than 35 years, 86 incident CHD and 155 incident stroke cases were identified. The rate ratios of hyperuricemia ranged between 2.00 and 3.96, with higher risk ratios in women than in men. The rate differences and population attributable fractions were also higher in women than in men, implying that women had high risk of uric acid on cardiovascular events. After adjustment for age effect, time-dependent uric acid was associated with significant CHD risk in both genders (hazard risk [HR] 1.43, 95% CI: 1.10-1.87 in men and HR 1.22, 95% CI: 1.03-1.44 in women). But the magnitude of hazard risks decreased after adjusting more atherosclerotic risk factors for CHD. For stroke event, the age-adjusted hazard risk of time-dependent continuous uric acid level was 1.23 (95% CI: 1.00-1.54) in men and 1.36 (95% CI: 1.05-1.75) in women. Multiple adjustment by risk factors demonstrated that uric acid was still a significant predictor for stroke in women (HR 1.32, 95% CI: 1.00-1.73). The similar hazard risk patterns existed for binary categories of hyperuricemia. Subgroup analyses demonstrated uric acid had significant risk only in hypertension and metabolic syndrome subgroups, not in their counterparts. We concluded that uric acid, in the baseline and time-dependent variables, could predict cardiovascular events in the community of relatively low CHD but high stroke risk in Taiwan.


Risk factors for diabetes insipidus in langerhans cell histiocytosis.
Diabetes insipidus (DI) is the most frequent central nervous system (CNS)-related permanent consequence in Langerhans cell histiocytosis (LCH), which mostly requires life-long hormone replacement therapy. In an attempt to define the population at risk for DI, 1,741 patients with LCH registered on the trials DALHX 83 and DALHX 90, LCH I and LCH II were studied. Overall 212 of 1,741 patients (12%) was reported to have DI. In 102 of 1,741 patients (6%) DI was present at diagnosis of LCH. One thousand one hundred eighty three of 1,539 patients without DI at diagnosis had follow up information. One hundred ten of these (9%) later developed DI. The risk of developing DI was 20% at 15 years after diagnosis. Multisystem disease patients at diagnosis carried a 4.6-fold risk for DI compared to single system patients. Craniofacial lesions, in particular in the "ear," "eye," and oral region were associated with a significantly increased risk for DI (relative hazard rate, RHR 1.7), independent of the extent of disease. No influence of the duration of therapy could be determined, but the duration of initial disease activity (RHR 1.5) and the occurrence of reactivations (RHR 3.5) significantly increased the risk for DI. Patients with multisystem disease and craniofacial involvement at diagnosis, in particular of the "ear," "eye," and the oral region carry a significantly increased risk to develop DI during their course. This risk is augmented when the disease remains active for a longer period or reactivates.


Expression of osteopontin mRNA in normal and stone-forming rat kidney.
Human urine contains several macromolecules which inhibit calcium oxalate crystallization. Osteopontin (or uropontin), a secreted phosphoglycoprotein with the amino acid sequence Arg-Gly-Asp (RGD) and high affinity to hydroxyapatite, is one such inhibitor. To investigate the action of this protein on renal stone formation, the expression osteopontin gene in normal and chemically induced urolithiasis rat kidney was compared at both mRNA and protein levels. Northern blot analysis shown a significant increase of osteopontin mRNA level in stone-forming rat kidney compared with normal ones. In an in situ hybridization study, we localized the transcripts of the osteopontin gene in epithelial cells of both distal and collective tubules, and found a remarkably strong signal in stone-forming rats. The amount and distribution of the protein in kidney from immunocytochemistry staining showed the same pattern as seen in situ hybridization. These findings indicate that osteopontin may be an important macromolecule in the normal endogenous defence against the formation of urinary calculi.


Evaluation of dissipation gradients of polycyclic aromatic hydrocarbons in rice rhizosphere utilizing a sequential extraction procedure.
The aim of this study was to evaluate the spatial dissipation gradient of PAHs, including phenanthrene, pyrene, and benzo[a]pyrene, with various bioavailability represented with sequential extraction. Dissipation rates of PAHs in the rhizosphere were greater than those in the bulk soil. The n-butanol extracted fraction showed a general trend of dissipation during phytoremediation. Moreover, the formation of bound PAH residues was inhibited in the rhizosphere. While concerning the PAH toxicity, the reduction rates of PAH toxicity were significantly greater than total soil PAH concentrations. Microbial biomass was the highest at four mm away from the root surface. However, the PAH dissipation rates were the highest at one mm and two mm away from the root surface in high and low PAH treatments, respectively. These results suggest that rhizoremediation with rice is a useful approach to reduce the toxicity of PAHs in soil.


[Repair of chondral defects of the knee using a combination of autologous chondrocytes and osteochondral allograft--an animal model. Part I: in vitro culture of autologous chondrocytes].
In the study we used in vitro cultivated autologous chondrocytes in combination with osteochondral allografts for the treatment of local defects of articular cartilage on the animal model (rabbit). Chondrocytes for in vitro cultivation were harvested by biopsy of articular cartilage of rabbit. For the monolayer cultivation we used Nutrient mix F 12 (Gibco BRL) with addition of Lascorbic acid (50 micrograms/ml, Sigma) and insulin-trasferin-selenium (A 6.26 micrograms/ml, Gibco BRL), 20% of fectal serum (Gibco BRL) and antibiotic antimycotic solution (Gibco BRL). Cultivation of chondrocytes took place at 37 degrees in the atmosphere of 5% CO2. Multiplied chondrocytes re-suspended in fibrin glue in combination with two osteochondral allografts were used for the reparation of artificial defect of the rabbit cartilage. For the analysis of collagen type II in the cultivation medium we used the principle of salting out by 30% ammonium sulphate and subsequent pepsinization in an acid environment with a repeated salting out by means of 2M of NaCl. Precipitates were dissolved in 5.0 M of acetic acid and used for SDS PAGE and immunoblotting. As a detection system we used ECL (Amersham/Pharmacia Biotech). The final average number of chondrocytes multiplied by monolayer cultivation was 1.10(5). The presence of collagen of type II has proved the preservation of the original phenotype of chondrocytes during cultivation. Bioengineering use of cell and tissue cultivation provides new options of the treatment of defect of connective tissue. Transplantation of autologous chondrocytes in combination with osteochondral allografts is on the basis of our results obtained so far a promising therapy. The aim of our work was an ex vivo expansion of autologous chondrocytes for the purpose of cell transplantation.


The effects of task difficulty, background noise and noise reduction on recall.
In the present study, we investigated whether varying the task difficulty of the Sentence-Final Word Identification and Recall (SWIR) Test has an effect on the benefit of noise reduction, as well as whether task difficulty predictability affects recall. The relationship between working memory and recall was examined. Task difficulty was manipulated by varying the list length with noise reduction on and off in competing speech and speech-shaped noise. Half of the participants were informed about list length in advance. Working memory capacity was measured using the Reading Span. Thirty-two experienced hearing aid users with moderate sensorineural hearing loss. Task difficulty did not affect the noise reduction benefit and task difficulty predictability did not affect recall. Participants may have employed a different recall strategy when task difficulty was unpredictable and noise reduction off. Reading Span scores positively correlated with the SWIR test. Noise reduction improved recall in competing speech. The SWIR test with varying list length is suitable for detecting the benefit of noise reduction. The correlation with working memory suggests that the SWIR test could be modified to be adaptive to individual cognitive capacity. The results on noise and noise reduction replicate previous findings.


Pharmacokinetics and efficacy of intraocular flurbiprofen.
Intravitreal delivery of non-steroidal anti-inflammatory drugs could be an effective way to treat macular edema caused by posterior segment inflammation. In this study, we evaluated the intravitreal bioavailability and anti-inflammatory efficacy of flurbiprofen in rabbit eyes. For pharmacokinetics, 0.1 ml of 7.66 mg/ml flurbiprofen solution was injected intravitreally and vitreous drug levels were analyzed at specific time points using LC-MS technique. For efficacy, 100 ng lipopolysaccharide of E.coli was injected intravitreally in rabbits to induce inflammation. The animals were separated in three groups and received intraocular flurbiprofen, dexamethasone and PBS to serve as control. Complete ocular examination and total cell count in aqueous fluid were determined to evaluate the extent of inflammation. Eyes were then enucleated for histopathology analysis. The efficacy in the uveitis model was determined by clinical signs of inflammation, total leukocyte count and histology findings. No adverse events were observed during pharmacokinetic assessment. No signs of inflammation, hemorrhage or retina detachment were detected. The recovery of flurbiprofen from vitreous samples was 92.6%. The half-life of flurbiprofen was estimated to be 1.92 h with an elimination constant rate (K) of 0.36. Treatment with intraocular injections of flurbiprofen and dexamethasone significantly reduced total leukocyte count in a manner comparable to dexamethasone [reduction of 96.84% (p < 0.05) and 97.44% (p < 0.05), respectively]. Histologic studies demonstrated significantly less signs of ocular inflammation after flurbiprofen injection compared to control eyes. Flurbiprofen is effective in suppressing inflammation in this experimental uveitis model. In our experimental setting, intravitreal flurbiprofen seem to have a therapeutic result comparable to dexamethasone. However, the half-life of the drug remains short, necessitating further research to prolong its presence in the vitreous cavity.


Transport of maternal[3H]melatonin to suckling rats and the fate of [3H]melatonin in the neonatal rat.
The question of whether maternal melatonin could be transported in milk to suckling rats was investigated because melatonin is probably not produced in these animals during the first 10 days of life. [3H]Melatonin was found to be rapidly transferred from the maternal circulation into lactating mammary tissue, and the stomach of each suckling rat was found to contain [3H]melatonin. To study the fate and tissue distribution of [3H]melatonin originating in the neonatal stomach, suckling rats were given [3H]melatonin by stomach tube; [3H]melatonin was recovered from plasma and seven tissues, including brain, 15 and 60 min later. The general tissue distribution of [3H]melatonin was similar to that found in adult rats. The major [3H]melatonin metabolites in the urine of suckling rats, as the adult rats, were the conjugates of 6-hydroxy-melatonin.


Insulin sensitivity, insulinemia, and coronary artery disease: the Insulin Resistance Atherosclerosis Study.
The aim of this study was to evaluate whether low insulin sensitivity (Si) measured using a modified frequently sampled intravenous glucose tolerance test with minimal model analysis is associated with coronary artery disease (CAD) independent of other cardiovascular risk factors. We studied 1,482 women and men, age 40-69 years old, African American (28%), Hispanic (34%), or non-Hispanic white (38%), with normal (45%), impaired (23%), or diabetic (32%) glucose tolerance. CAD defined as confirmed past myocardial infarction, coronary artery bypass graft, coronary angioplasty, or presence of a major Q-wave was found in 91 participants. The odds ratio (OR) for CAD was greatest among individuals in the two lowest quintiles of Si (2.4, 95% CI 1.0-5.6 and 4.7, 2.1-10.7) compared with the highest Si quintile. After adjusting for demographic and cardiovascular risk factors, a decrement from the 75th to 25th percentile in Si was associated with a 56% increase in CAD (P=0.028). Similar increments in fasting or 2-h insulin levels were associated with, respectively, only 15 (NS) and 3% (NS) increases in CAD. The association between Si and CAD was partially mediated by insulin, HDL cholesterol and triglyceride levels, hypertension, diabetes, and obesity, but not LDL cholesterol or cigarette smoking. Low Si is associated with CAD independently of and stronger than plasma insulin levels. Part of the association is accounted for by dyslipidemia, hypertension, diabetes, and obesity.


Extirpation of alternative prey during a small rodent crash.
We document two episodes, in different years, of Barn Owls (Tyto alba) preying on a winter population of Burrowing Owls (Athene cunicularia) on a southern California island. The predation in each case followed a marked shift in the diet of the Barn Owls, due to the cyclic decline of their normal small mammal prey. Heavy predation in the first year resulted in the extirpation of the Burrowing Owls on the island. Such heavy predation on alternative prey species is commonly reported in cyclic predator-prey systems, however this is the first documented case of extirpation of the alternative prey. Complete elimination of any prey species by terrestrial predators is, in fact, very rare.


Comparison of central corneal thickness measurements by Pentacam, noncontact specular microscope, and ultrasound pachymetry in normal and post-LASIK eyes.
To compare central corneal thickness (CCT) measurements taken with Pentacam, noncontact specular microscope (NCSM), and ultrasound pachymetry (US) in normal and post-laser in situ keratomileusis (LASIK) eyes and to assess the agreement between the three devices. Prospective clinical trial. Central corneal thickness (CCT) was measured in 94 eyes of normal volunteer and in 72 eyes of post-LASIK patients. Measurements were made with the three devices. In normal eyes, the mean (±SD) CCT taken with Pentacam, NCSM, and US was 552.6 ± 36.8 μm, 511.9 ± 38.6 μm, and 533.3 ± 37.9 μm, respectively. The average values of CCT taken with the three instruments were significantly different. In post-LASIK eyes the mean CCT with Pentacam, NCSM, and US was 483.02 ± 6.03 μm, 450.7 ± 5.3 μm, and 469.5 ± 5.8 μm, respectively. The average values of CCT taken were significantly different for Pentacam vs. NCSM (P = 0.046) and Pentacam vs. US (P = 0.02), but not significant for NCSM vs. US (P = 0.352). The Bland and Altman method for assessing clinical agreement between 3 instruments showed that in normal eyes, the mean values and paired differences of the three CCT devices were found to be statistically independent. In post-LASIK eyes, there was significant association between the difference and the mean of the Pentacam and NCSM, and US and NCSM. The three devices cannot be used interchangeably in normal and post-LASIK eyes. Pentacam tends to give significantly thicker reading than ultrasound pachymetry.


The augmentation of tumor-specific immunity by virus help. I. Demonstration of vaccinia virus-reactive helper T cell activity involved in enhanced induction of cytotoxic T lymphocyte and antibody responses.
C3H/He mice were immunized to vaccinia virus by inoculating i.p. viable virus. Their spleen cells (SC) were tested for vaccinia virus-reactive helper T cell activity capable of augmenting (a) anti-trinitrophenyl (TNP) cytotoxic T lymphocyte (CTL) response generated from unprimed C3H/He SC (responding cells) or (b) anti-TNP antibody response generated from TNP-primed C3H/He SC (responding cells) by the stimulation with syngeneic SC infected with vaccinia virus and subsequently modified with TNP (virus-self-TNP). The results demonstrate that cultures of responding cells plus 850 rds X-irradiated vaccinia virus-primed SC failed to enhance anti-TNP CTL or plaque-forming cell (PFC) responses when in vitro stimulation was provided by either virus-self or TNP-self alone. In contrast, these cultures resulted in appreciable augmentation of CTL and PFC responses when stimulated by virus-self-TNP. Such a helper activity provided by vaccinia virus-primed SC was revealed to be T cell mediated and antigen specific. These results are discussed in the context of (a) nature of virus helper antigens, (b) mechanism of help and (c) potential of virus help in augmenting CTL and antibody responses to tumor antigens.


Impact of keratoconus, cross-linking and cross-linking combined with photorefractive keratectomy on self-reported quality of life.
To assess the effect of stage 1 keratoconus (KC) and of the 2 prevalent KC therapeutic options: (1) corneal collagen cross-linking (CXL) and (2) CXL combined with topography-guided photorefractive keratectomy (t-PRK) on self-reported quality of life (QOL) by means of the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ 25). Thirty-two patients with bilateral KC stage 1 (KC group) and best-corrected visual acuity of 20/20 in both eyes were prospectively recruited. Of them, 19 KC patients underwent typical CXL treatment (CXL group), whereas 13 underwent CXL combined with t-PRK treatment (tCXL group). Only the eye with the most advanced condition received the treatment. Subjects responded to the NEI-VFQ 25 1 day before the treatment and 1 year postoperatively. Thirty-nine age-matched contact lens users formed the control group. NEI-VFQ 25 subscale and total scores were associated with spherical equivalent, mean keratometry, and a series of Scheimpflug imaging-derived corneal variance indexes by means of the Spearman correlation coefficient and multivariate linear regression analysis. Preoperatively, significant differences were detected between the KC group and the control group in VFQ 25 total and all subscale scores (P < 0.05), except "general health," "color vision," and "peripheral vision" domains. According to the multivariate linear regression analysis, the index of height decentration was the most significant predictor of VFQ 25 total score (b = 0.943; P = 0.016). Postoperatively, significant differences were detected in "mental health" and "dependency" VFQ 25 domains for both the CXL and tCXL groups (P = 0.05). Furthermore, the tCXL group demonstrated significant differences in the "near activities" (P = 0.04), "role limitations" (P = 0.02), and "driving" (P < 0.01) subscale scores. Our results suggest that KC exerts a significant impact on KC patients' QOL, even in its early stages with normal best-spectacle-corrected visual acuity. Moreover, both CXL and CXL combined with t-PRK seem to exert a beneficial impact on self-reported QOL, suggesting that they should be applied as soon as possible.


Microwave ablation versus parathyroidectomy for the treatment of primary hyperparathyroidism: a cohort study.
To compare the clinical outcomes between microwave ablation (MWA) and parathyroidectomy (PTX) for the treatment of primary hyperparathyroidism (pHPT). This retrospective study enrolled 212 patients with pHPT treated by either MWA (MWA group) or PTX (PTX group) from January 2015 to October 2020. The baseline data were balanced through propensity score matching. Clinical cure was evaluated by the Kaplan-Meier method and compared between the MWA and PTX groups. The risk factors related to persistent or recurrent pHPT were screening out using a Cox proportional hazards regression model. After propensity score matching, a total of 174 patients were enrolled in the present study, with 87 patients in each group. During the follow-up period (median, 28.5 months), there were no differences between the two groups regarding the clinical cure (hazard ratio, 1.71; 95% confidence interval: 0.81-3.62; p = .155), persistent pHPT rate (13.8% vs. 10.3%, p = .643), recurrent pHPT rate (6.9% vs. 3.4%, p = .496), or major complications (6.9% vs. 3.4%, p = .496). MWA resulted in a shorter procedure time (30 min vs. 60 min), smaller incision length (0.1 cm vs. 7 cm) and slightly higher costs (25745 CNY vs. 24111 CNY) (all p < .001). High levels of preoperative intact parathyroid hormone (p = .01) and multiple pHPT nodules (p < .001) were independent risk factors for recurrent and persistent pHPT in the two groups. MWA and PTX have comparable clinical outcomes for pHPT. MWA has a shorter procedure time and smaller incision length. • There were no differences in terms of clinical cure, persistent pHPT, recurrent pHPT, or major complications between MWA and PTX in the treatment of pHPT. • MWA is minimally invasive and results in a shorter procedure time. • Multiple nodules and high levels of iPTH were the independent risk factors for recurrent and persistent pHPT.


Magnetic resonance imaging of discrete and conglomerate retroperitoneal lymph node masses.
In the identification of discrete and conglomerate retroperitoneal lymph node masses, MRI and CT performed equally well. No specific MRI characteristics were identified.


An in-vitro profile of the action of four antimalarials on indigenous cases of Plasmodium falciparum malaria in Karnataka.
In view of the emergence of chloroquine resistant Plasmodium falciparum from more and more geographical areas profiling of the responses to other available antimalarials by in vitro methods have become essential. A preliminary study undertaken in two Primary Health Centres of Karnataka State, India show the presence of strains of P. falciparum resistant to chloroquine and amodiaquine. The response for amodiaquine was poor as compared to chloroquine. The isolates were, however, sensitive to mefloquine and quinine.


Phorbol esters inhibit fibroblast growth factor-2-stimulated fibroblast proliferation by a p38 MAP kinase dependent pathway.
Treatment of fibroblasts with the phorbol ester, 12-O-tetradecanoyl phorbol 13-acetate (TPA), specifically inhibits fibroblast growth factor-2 (FGF-2) induced proliferation. TPA treatment has little or no effect on FGF receptor activation but specifically inhibits the activation of p38 MAPK but not other downstream signaling pathways implicated in cell proliferation. p38 MAPK was recently shown to be required for the FGF-2-stimulated proliferation of fibroblasts. The effect of TPA on both p38 MAPK activation and cell proliferation can be reversed by treatment with the PKC inhibitor Go6983. The TPA-mediated inhibition of p38 MAPK activation requires phosphatase activity and is at least partially mediated by ERKs since it is reduced by treatment with the MEK inhibitor PD98059. In contrast, the FGF-2-stimulated differentiation of PC12 cells, which express the same FGF receptor as Swiss 3T3 fibroblasts, is not affected by TPA treatment, consistent with a lack of involvement of p38 MAPK activity in this process. These data indicate that the effects of TPA treatment on cellular function are not only cell type but also stimulus specific and are dependent upon the distinct pathways activated downstream of each stimulus.


Significance of Distal Runoff Score as a Key Influencer on Clinical Outcomes after Endovascular Interventions for Superficial Femoral Artery Disease.
Endovascular therapy (EVT) is being adopted by many surgeons as a suitable first choice in the treatment of most femoropopliteal disease when clinically indicated. However, there are multiple factors affecting the outcome of EVT including the anatomy of lesions and distal runoff status. The evidence of runoff effect on the outcome of superficial femoral artery (SFA) interventions is still scarce and not well studied in the current literature. The aim of this study was to investigate the effect of runoff score on the outcomes of SFA endovascular interventions. Retrospective analysis was carried out on prospectively collected data on patients who underwent SFA endovascular intervention for critical limb ischemia (CLI) in a single tertiary center. Patients with Rutherford categories 4, 5, and 6 who did not have any previous vascular interventions were included in the study. The modified SVS runoff score was used after calculating scores from popliteal and all tibial vessels. Runoff was stratified into good (score <5), compromised (score 5-10), and poor (score >10). Amputation-free survival, patency rates, and overall survival were compared between all groups at 5 years. Between 2011 and 2018, 254 procedures were performed in 220 patients. Technical success was >92%; 66 patients required SFA stents, and 55 had concomitant tibial angioplasty. There was no significant difference between good, compromised, or poor runoff groups regarding complication rates, with 3.5% overall perioperative mortality (5 cases in the compromised group and 4 in the poor runoff group). A runoff score of <5 was associated with significantly marked clinical improvement (P < 0.001). Patency rates were significantly worse in the compromised and poor runoff groups, with 5-year cumulative primary patency rates of 80%, 50%, and 22% in the good, compromised, and poor runoff groups, respectively (P < 0.001). Amputation-free survival worsened as the runoff got poorer with 98%, 91%, and 78% in the good, compromised, and poor runoff groups, respectively, at 5 years (P < 0.001). SFA stenting and concomitant tibial angioplasty led to slight improvement in patency rates in the poor runoff group. Poor runoff with a score of >10 was associated with significantly reduced amputation-free survival and patency rates at 5 years in patients undergoing SFA endovascular intervention for CLI. Patients with a runoff score of <5 showed marked clinical improvement postoperatively when compared with patients with a runoff score of ≥5.


Unusual pattern of metabolites in the urine of child with tyrosinemia: glyceraldehyde.
An unusual metabolite has been found in the acidic fraction of the urine of a child with tyrosinemia. This compound has been identified as glyceraldehyde, in addition to phenylacetic acid and p-hydroxybenzaldehyde, on the basis of gas chromatograph-mass spectral data and comparison with authentic samples.


Acute mastoid abscess and cholesteatoma.
A 10-year review of acute mastoid abscess treated surgically in Belfast revealed a total of 24 cases, 12 of which were found to have an underlying cholesteatoma. The surgical management of these 12 cases is outlined but despite a desire to maintain an intact canal wall, 9 of them to date have ended up with an open cavity. The danger of conservative management and the possible association between acute mastoid abscess and cholesteatoma, especially in developed countries, is stressed.


The Clinical Challenge of Idiopathic Cytopenias of Undetermined Significance (ICUS) and Clonal Cytopenias of Undetermined Significance (CCUS).
To review terminology, diagnostic algorithms, and clinical outcomes for patients with unexplained blood cytopenias. Patients with cytopenias that remain unexplained after organized diagnostic testing can be described as having "idiopathic cytopenias of undetermined significance" (ICUS). Patients with unexplained cytopenias have a risk of progression to clonal myeloid neoplasms, including myelodysplastic syndromes (MDS). If a somatic mutation in a gene associated with leukemia is detectable in hematopoietic tissue, especially if multiple mutations with a high (> 10%) variant allele frequency are present, the risk of progression to frank neoplasia is greater than if such mutations are not detected. These patients can be described with the term, "clonal cytopenias of undetermined significance" (CCUS). CCUS patients have a natural history similar to lower-risk MDS. For patients with unexplained cytopenias, longitudinal follow-up including serial monitoring of blood counts is appropriate in view of the progression risk. Genetic testing may aid in risk stratification.


The process of methylglyoxal-induced retinal capillary endothelial cell degeneration in rats.
Methylglyoxal, a highly reactive dicarbonyl compound, is increased and accumulated in patients with diabetic mellitus. Methylglyoxal forms advanced glycation end products (AGE), contributing to the pathogenesis of diabetic complications, including diabetic retinopathy. Recent studies have shown that methylglyoxal induces diabetic retinopathy-like abnormalities in retinal vasculature. In this study, we investigated the processes and mechanisms of methylglyoxal-induced retinal capillary endothelial cell degeneration in rats. Morphological changes in vascular components (endothelial cells, pericytes, and basement membranes) were assessed in the retinas 2, 7, and 14 days after intravitreal injection of methylglyoxal. Intravitreal methylglyoxal injection induced retinal capillary endothelial cell degeneration in a dose- and time-dependent manner. Changes in the shape and distribution of pericytes occurred before the initiation of capillary regression in the retinas of methylglyoxal-injected eyes. The receptor for AGEs (RAGEs) antagonist FPS-ZM1, and the matrix metalloproteinase (MMP) inhibitor GM6001 significantly attenuated methylglyoxal-induced capillary endothelial cell degeneration. FPS-ZM1 failed to prevent pathological changes in pericytes in methylglyoxal-injected eyes. In situ zymography revealed that MMP activity was enhanced at sites of blood vessels with reduced pericyte coverage in methylglyoxal-injected eyes. These results suggest that intravitreal methylglyoxal injection induces pathological changes in pericytes before the initiation of capillary endothelial cell degeneration via an AGE-RAGE-independent pathway. The capillary endothelial cell degeneration is mediated by activating the AGE-RAGE pathway and increasing MMP activity in endothelial cells by impairing pericyte function in the retina.


In vivo markers of oxidative stress and therapeutic interventions.
Over the last decade, significant data has accumulated to suggest that biomarkers of oxidative stress accurately reflect the presence of cardiovascular risk factors, the extent of cardiovascular disease (CVD), and cardiovascular outcomes. This cumulative evidence has supported the approval of several of these biomarkers for clinical applications. For example, lipoprotein-associated phospholipase A(2) (Lp-PLA2) and myeloperoxidase (MPO) mass assays are now available to assist clinicians in determining overall cardiovascular risk in asymptomatic patients thought to be at increased risk or in patients with cardiovascular symptoms. However, it is not yet firmly established whether and to what extent these oxidative biomarkers reflect changes in response to therapeutic interventions. This article reviews the latest data on MPO, isoprostanes, oxidized low-density lipoprotein, oxidized phospholipids, and Lp-PLA2 biomarker assays, and it assesses their role in reflecting therapeutic interventions to treat CVD.


KBa(2)InAs(3) with coexisting monomers of [In(2)As(7)](13-) and their one-dimensional polymers.
The title compound was made by fusion of a stoichiometric mixture of the pure elements. The structure (orthorhombic, Cmc2(1), Z = 16, a = 10.129(2) A, b = 25.208(4) A, c = 13.884(3) A) is made of isolated units of [In(2)As(7)](13-) and a polymer chain of [In(2)As(5)](7-) made of the same units. According to magnetic measurement, KBa(2)InAs(3) is a closed-shell compound, a Zintl phase.


How to Clear Polytrauma Patients for Fracture Fixation: Results of a systematic review of the literature.
Early patient assessment is relevant for surgical decision making in severely injured patients and early definitive surgery is known to be beneficial in stable patients. The aim of this systematic review is to extract parameters indicative of risk factors for adverse outcome. Moreover, we aim to improve decision making and separate patients who would benefit from early versus staged definitive surgical fixation. Following the PRISMA guidelines, a systematic review of peer-reviewed articles in English or German language published between (2000 and 2022) was performed. The primary outcome was the pathophysiological response to polytrauma including coagulopathy, shock/haemorrhage, hypothermia and soft tissue injury (trauma, brain injury, thoracic and abdominal trauma, and musculoskeletal injury) to determine the treatment strategy associated with the least amount of complications. Articles that had used quantitative parameters to distinguish between stable and unstable patients were summarized. Two authors screened articles and discrepancies were resolved by consensus. Quantitative values for relevant parameters indicative of an unstable polytrauma patient were obtained. The initial systematic search using MeSH criteria yielded 1550 publications deemed relevant to the following topics (coagulopathy (n = 37), haemorrhage/shock (n = 7), hypothermia (n = 11), soft tissue injury (n = 24)). Thresholds for stable, borderline, unstable and in extremis conditions were defined according to the existing literature as follows: Coagulopathy; International Normalized Ratio (INR) and viscoelastic methods (VEM)/Blood/shock; lactate, systolic blood pressure and haemoglobin, hypothermia; thresholds in degrees Celsius/Soft tissue trauma: traumatic brain injury, thoracic and abdominal trauma and musculoskeletal trauma. In this systematic literature review, we summarize publications by focusing on different pathways that stimulate pathophysiological cascades and remote organ damage. We propose that these parameters can be used for clinical decision making within the concept of safe definitive surgery (SDS) in the treatment of severely injured patients.


Immunomodulating activity of DW-116, a new quinolone antibiotic.
DW-116, (1-(5-fluoro-2-pyridyl)-6-fluoro-7-(4-methyl-1-piperazinyl)-1, 4-dihydro-4-oxoquinoline-3-carboxylic acid hydrochloride), is a new quinolone antibiotic with a broad antibacterial spectrum against G(+) and G(-) bacteria. DW-116 was evaluated for the immunomodulating activities, which is one of the efforts to investigate the mechanism of action related to the good in vivo antibacterial efficacy. The results of in vitro studies revealed there was no statistically significant increase in B and T lymphocyte proliferation. But the results of in vivo studies showed that the number of plaque forming cells (PFC), the amount of polyclonal antibodies and delayed-type hypersensitivity (DTH) were significantly increased after the repeat administration with 12 and 60 mg/kg of DW-116. Taken together, these results proposed that immunostimulating effect of DW-116 could be one of the action mechanisms for demonstrating in vivo antibacterial activities under these experimental conditions.


Predicting proteolytic sites in extracellular proteins: only halfway there.
Many secretory proteins are synthesized as inactive precursors that must undergo post-translational proteolysis in order to mature and become active. In the current study, we address the challenge of sequence-based discovery of proteolytic sites in secreted proteins using machine learning. The results revealed that only half of the extracellular proteolytic sites are currently annotated, leaving over 3600 unannotated ones. Furthermore, we have found that only 6% of the unannotated sites are similar to known proteolytic sites, whereas the remaining 94% do not share significant similarity with any annotated proteolytic site. The computational challenges in these two cases are very different. While the precision in detecting the former group is close to perfect, only a mere 22% of the latter group were detected with a precision of 80%. The applicability of the classifier is demonstrated through members of the FGF family, in which we verified the conservation of physiologically-relevant proteolytic sites in homologous proteins.


Bioassays to Evaluate the Resistance of Whole Plants to the Herbivorous Insect Thrips.
Thrips are tiny, cell-content-feeding insects that are a major pest on crops and ornamentals. Besides causing direct feeding damage, thrips may also cause indirect damage by vectoring tospoviruses. Novel resistance mechanisms to thrips need to be discovered and validated. Induction of jasmonic acid-dependent defenses has been demonstrated to be essential for resistance to thrips, but underlying mechanisms still need to be discovered. For this, it is vital to use robust plant-thrips assays to analyze plant defense responses and thrips performance. In recently developed high-throughput phenotyping platforms, the feeding damage that is visible as silver spots, and the preference of thrips in a two-choice setup is assessed, using leaf discs. Here, we describe whole-plant thrips assays that are essential for (1) validation of findings obtained by the leaf disc assays, (2) assessment of longer-term effects on thrips feeding success and fecundity, (3) determination of spatial-temporal effects induced by primary thrips infestation on a secondary attack by thrips or other insects or pathogens, and (4) assessment of gene expression and metabolite changes. We present detailed methods and tips and tricks for (a) rearing and selection of thrips at different developmental stages, (b) treatment of the whole plant or an individual leaf with thrips, and (c) determination of feeding damage and visualization of thrips oviposition success in leaves.


Abundant GABAergic innervation of rat posterior pituitary revealed by inhibition of GABA-transaminase.
An antibody against gamma-aminobutyric acid (GABA) was used to identify GABAergic elements immunocytochemically in the rat posterior pituitary. In order to increase the intracellular concentration of GABA, rats were treated with the GABA-transaminase inhibitor gamma-vinyl-GABA (GVG). Light-microscopic observations of Vibratome and semithin sections revealed the presence of numerous immunoreactive nerve fibers throughout the neural lobe; the mean number and length of these fibers increased by 90% after GVG treatment. Electron microscopy demonstrated the immunostained axons to be of small diameter. The reaction product was confined to small vesicles. No immunostaining occurred in pituicytes. The richness of the GABAergic innervation of the neural lobe contrasts with previous reports using antibodies against glutamate decarboxylase and supports the idea that GABA participates in the presynaptic control of neurosecretion.


Radiological management and challenges of the twin earthquakes of February 6th.
Two major earthquakes measuring 7.8 and 7.7 on the Richter scale struck Turkey and Northern Syria on February 6, claiming more than 50,000 lives. In such an unprecedented disaster, radiologists were confronted with very critical tasks of stepping out of the routine reporting process, performing radiological triage, managing acute adverse events, and optimizing imaging protocols. In our experience, radiologists can take three different positions in such disasters: (1) in the scene of the disaster, (2) serving in teleradiology, and (3) working in tertiary hospital for transported patients. With this article, we aimed to describe the challenges radiologists face on the three main fronts and how we manage these challenges.