Development of pluripotent stem cells for vascular therapy.
Peripheral arterial disease (PAD) is characterized by reduced limb blood flow due to arterial obstruction. Current treatment includes surgical or endovascular procedures, the failure of which may result in amputation of the affected limb. An emerging therapeutic approach is cell therapy to enhance angiogenesis and tissue survival. Small clinical trials of adult progenitor cell therapies have generated promising results, although large randomized clinical trials using well-defined cells have not been performed. Intriguing pre-clinical studies have been performed using vascular cells derived from human embryonic stem cells (hESC) or human induced pluripotent stem cells (hiPSCs). In particular, hiPSC-derived vascular cells may be a superior approach for vascular regeneration. The regulatory roadmap to the clinic will be arduous, but achievable with further understanding of the reprogramming and differentiation processes; with meticulous attention to quality control; and perseverance.


A new approach for simulating inhomogeneous chemical kinetics.
In this paper, inhomogeneous chemical kinetics are simulated by describing the concentrations of interacting chemical species by a linear expansion of basis functions in such a manner that the coupled reaction and diffusion processes are propagated through time efficiently by tailor-made numerical methods. The approach is illustrated through modelling [Formula: see text]- and [Formula: see text]-radiolysis in thin layers of water and at their solid interfaces from the start of the chemical phase until equilibrium was established. The method's efficiency is such that hundreds of such systems can be modelled in a few hours using a single core of a typical laptop, allowing the investigation of the effects of the underlying parameter space. Illustrative calculations showing the effects of changing dose-rate and water-layer thickness are presented. Other simulations are presented which show the approach's capability to solve problems with spherical symmetry (an approximation to an isolated radiolytic spur), where the hollowing out of an initial Gaussian distribution is observed, in line with previous calculations. These illustrative simulations show the generality and the computational efficiency of this approach to solving reaction-diffusion problems. Furthermore, these example simulations illustrate the method's suitability for simulating solid-fluid interfaces, which have received a lot of experimental attention in contrast to the lack of computational studies.


Sulfaquinoxaline Toxicosis in a Juvenile Broiler Breeder Flock.
A flock of 50,000 28-day-old broiler breeder chickens experienced an elevated mortality event. Chickens from that flock, five pullets and six cockerels, were submitted for diagnostic investigation. Necropsy revealed bacterial septicemia with fibrinous polyserositis in the majority of the birds while two cockerels had coccidial typhlitis. Because sulfadimethoxine was not available at the time, sulfaquinoxaline (SQ) was prescribed at label dosage with water treatment for 2 days, followed by 3 days of no medication, followed by 2 days of medication. The mortality rose dramatically 9 days after the last treatment. Lesions at that time consisted of skin discoloration, subcutaneous petechiation, and enlarged pale kidneys. Mortality remained elevated for 14 days. Analysis of blood, kidney, and liver revealed elevated levels of SQ. Recalculation of dosage, water consumption, amount of drug administered, remaining drug stock, and concentration of supplied SQ were analyzed and determined to be as predicted.


[Development of swimming behavior in mice as a behavioral test in toxicology].
The development of the swimming behaviour in mice is described by 7 stages. The inbred strains and hybrids investigated showed differences in the progress of this development. In comparing the swimming behaviour of offspring from Cyclophosphamid- treated and untreated dams temporal differences have been registered, too. The swimming test is thought to be a suitable behavioural test within embryotoxicological investigations.


Quantitative dynamic contrast-enhanced MRI of bone marrow perfusion at the proximal femur: influence of femoral head osteonecrosis risk factor and overt osteonecrosis.
To evaluate the MRI perfusion changes in patients with risk factors for osteonecrosis and normally appearing femoral heads prior to overt femoral head osteonecrosis. Fifty-eight patients (105 hips) were prospectively included in this ethics committee-approved study. There were 46 hips with no image anomalies and no risk factors for osteonecrosis of the femoral head (ONFH) risk factors, 38 with ONFH risk factors and no image abnormalities, and 21 with overt ONFH. All patients underwent DCE-MRI. Semi-quantitative (peak enhancement [PE], area under the curve [AUC], time to maximum enhancement [TME]) and quantitative perfusion parameters (volume plasma, KTRANS, and KEP) were calculated. Excessive alcohol consumption, corticosteroid use, and trauma were considered major risk factors for osteonecrosis of the femoral head. Measured at the femoral neck and compared to the healthy hips without OFNH risk factors, PE was significantly lower in the hips of patients with OFNH risk factors. Moreover, the difference was greater in females with risk factors, who presented significantly lower PE values (p = 0.0096). A PE threshold of 1.4% yielded a 92% sensitivity and 54% specificity for the presence of associated ONFH risk factors. The hips with overt OFNH compared to those with normally appearing showed an increase of PE of 45% in the neck (p < 0.014). Various epiphyseal femoral head perfusion parameters (PE, TME, AUC, and Ktrans) presented statistically significant differences in hips with ONFH and those without (p < 0.0001). DCE-MRI can identify perfusion marrow changes related to the presence of ONFH risk factors and adjacent to osteonecrosis areas. • Bone marrow perfusion changes may occur prior to overt ONFH and extend beyond the osteonecrosis area to the entire femoral head and neck. • Peak enhancement values were significantly reduced in patients with ONFH risk factors, compared to those without. • The presence of ONFH led to a significant increase in marrow perfusion adjacent to the osteonecrosis area.


Expression change of ezrin as a prognostic factor in primary osteosarcoma.
Osteosarcoma is a life-threatening malignancy that most often occurs in teenagers. Ezrin is a cytoskeleton linker protein that is actively involved in the metastatic capacity of cancer cells. In this study, we investigated the expression change of ezrin after preoperative chemotherapy and its prognostic value in patients with primary osteosarcoma. Ezrin mRNA expression level of initial biopsy specimens and resected tumor specimens after preoperative chemotherapy of 25 patients who had primary osteosarcoma with ezrin expression was detected by semiquantitative reverse transcription polymerase chain reaction (RT-PCR) to evaluate the expression change of ezrin. In addition, the prognostic factors and the relationship between the expression change of ezrin and the clinical characteristics were analyzed. Expression change of ezrin was found in 64% of all 25 patients. The expression change of ezrin had good relation with histology (P = 0.037), grade (P = 0.006), chemotherapy response (P = 0.017), and metastasis or recurrence (P = 0.041). The 2-year overall survival and event-free survival were associated with expression change of ezrin (P = 0.001 and P = 0.002, respectively) and response to preoperative chemotherapy (P = 0.001 and P = 0.012, respectively). Our findings suggest that expression change of ezrin is an independent positive prognostic factor in non-metastatic osteosarcoma.


Impact of chronic sub-lethal methylparaben exposure on cardiac hypoxia and alterations in neuroendocrine factors in zebrafish model.
Endocrine-disrupting chemicals have been shown to cause toxicity in different systems of the body including the endocrine, cardiovascular and nervous systems. This study aims to analyze the adverse effects of Methylparaben (MP) on cardiac functions, neurodevelopment, and behavior of zebrafish. Adult male and female zebrafish were exposed to MP for 30 days to study the toxicity effects. Zebrafish were grouped into control, solvent control, 1/10th (110 ppb), 1/100th, and 1/1000th (1 ppb) lethal concentration 50 of MP. Neurobehavioral assays, acetylcholinesterase (AChE) activity, serotonin levels, and expression of genes-Hypoxia-inducible factor 1 alpha, Neurotrophic Receptor Tyrosine Kinase, Paired box protein Pax-6, and tnnt2 were investigated in zebrafish. Results of the study showed more anxiety-like behavior in MP-treated female zebrafish when compared to males on chronic exposure. There was a dose-dependent reduction of AChE activity in both male and female zebrafish. Female zebrafish showed a dose-dependent increase in serotonin level on MP exposure while male zebrafish showed a dose-independent decrease in serotonin level. On MP exposure, there was also a dose-dependent dysregulation in the expression of cardiac hypoxia and neuronal differentiation-related genes in female zebrafish while a dose-independent change was observed in male zebrafish. Chronic MP exposure affects cardiac functions, neuronal functions, and behavior of zebrafish by exhibiting changes in AChE activity, serotonin levels, and altering the expression of genes related to cardiac hypoxia and neuronal differentiation even at sub-lethal doses.


Evaluation of 6 Patients with Genital Melanoma from Onset of Symptoms to Death: Evaluate the Factors Affecting the Prognosis of the Disease.
Genital melanoma is a rare but deadly cancer in women and the prognosis is often poor. This study assesses the impact of possible risk factors on the end prognosis of the patients, with the ultimate goal of improving survival of disease. This is a report of 6 patients diagnosed and treated as genital melanoma. Parameters reviewed included: age at diagnose, presenting symptoms, location size and Breslow depth of lesion, stage at diagnose, adjuvant therapies, hysterectomy and salpingo-oophorectomy, metastasis or recurrence in follow-up, chemotherapy for metastatic disease. The mean age at the time of diagnosis, was 44.67 years, the average size of lesion was 2.91 cm; the average Breslow depth of lesion was 1.93 mm. The mean interval between the onsets of symptoms to diagnosis was 16.7 months; the average life expectancy was 23.5 months. There is no significant relationship between the initial location of the lesion and prognosis (P: 0.98). Patients diagnosed in < 7 months, were in lower stages at diagnose (P: 0.018), and the survival of them was better (P: 0.035). Patients diagnosed in early stages had better survival at last (P: 0.035) Adjuvant radiotherapy improves survival markedly (P: 0.018). Hysterectomy and salpingo-oophorectomy had no significant effect on prognosis (P: 0.7). Chemotherapy in metastatic disease had no significant effect on prognosis (P: 0.46). The survival markedly improved if the disease diagnosed in a short distance from onset of symptoms and specially in early stages. Adjuvant radiotherapy can improve the survival significantly, but for the early hysterectomy and salpingo-oophorectomy and also for chemotherapy in metastatic disease, the impact on prognosis is uncertain, but positive.


Percent amino-acid identity thresholds are not necessarily conservative for predicting allergenic cross-reactivity.
International guidance on assessing amino-acid sequences for allergenic cross reactivity, such as that provided by Codex, relies on percent amino-acid identity across local alignments. Previous work has shown this approach to exhibit poor selectivity for true allergen cross-reactivity. Here we provide a hypothetical example illustrating that this approach is also not necessarily conservative in detecting high similarity across amino acid sequences, and thus, is not necessarily conservative in detecting potential allergenic cross reactivity among proteins. It is recommended that an established local-alignment bioinformatic tool like FASTA be used in conjunction with statistical measures of similarity to detect the risk of a protein cross-reacting with an allergen.


Lipopolysaccharide decreases bradykinin receptor-induced acidification responses in cultured bovine aortic endothelial cells.
The effects of bacterial lipopolysaccharide (Escherichia coli 0127-B8) on bradykinin receptor function in bovine aortic endothelial cells were investigated using a microphysiometer. Bradykinin and Lys(0)-desArg(10)-bradykinin produced concentration-dependent acidification responses with pEC(50) values of 8.87+/-0.20 and 9.78+/-0.08, respectively. These responses were competitively and selectively antagonised by the bradykinin B(2) receptor antagonist, icatibant and the bradykinin B(1) receptor antagonist, desArg(9)-Leu(8)-bradykinin, respectively. The non-peptide bradykinin B(2) receptor antagonist, FR173657 (0.3 and 3 nM), selectively antagonised bradykinin-induced acidification responses, causing rightward shifts of the concentration-response curves to bradykinin, but at the same time, significantly decreasing the maximum response. A preincubation with lipopolysaccharide (0.01 and 0.1 microg/ml) for 24 h caused a significant concentration-dependent decrease in maximal response to bradykinin (27.2+/-1.9 and 9.7+/-0.4% of control) and the bradykinin B(1) receptor agonist, Lys(0)-desArg(10)-bradykinin (59.0+/-7.14 and 25.3+/-7.8% of control), without affecting the EC(50). These results suggest that bradykinin B(1) receptors are constitutively expressed in cultured bovine aortic endothelial cells and that the microphysiometer provides a rapid, sensitive technique to characterise bradykinin receptors and investigate their regulation by cytokines. Interactions between bradykinin receptors and lipopolysaccharide may play a part in the cascade of deleterious effects that occur during septic shock.


Management of diabetes mellitus and associated cardiovascular risk factors in Brazil - the Brazilian study on the practice of diabetes care.
The Brazilian Study on the Practice of Diabetes Care main objective was to provide an epidemiological profile of individuals with type 1 and 2 diabetes mellitus (DM) in Brazil, concerning therapy and adherence to international guidelines in the medical practice. This observational, cross-sectional, multicenter study collected and analyzed data from individuals with type 1 and 2 DM attending public or private clinics in Brazil. Each investigator included the first 10 patients with type 2 DM who visited his/her office, and the first 5 patients with type 1 DM. A total of 1,358 patients were analyzed; 375 (27.6%) had type 1 and 983 (72.4%) had type 2 DM. Most individuals were women, Caucasian, and private health care users. High prevalence rates of hypertension, dyslipidemia and central obesity were observed, particularly in type 2 DM. Only 7.3% and 5.1% of the individuals with types 1 and 2 DM, respectively, had optimal control of blood pressure, plasma glucose and lipids. The absence of hypertension and female sex were associated with better control of type 1 DM and other cardiovascular risk factors. In type 2 DM, older age was also associated with better control. Female sex, older age, and absence of hypertension were associated with better metabolic control. An optimal control of plasma glucose and other cardiovascular risk factors are obtained only in a minority of individuals with diabetes. Local numbers, compared to those from other countries are worse.


Neuronal scaling rules for primate brains: the primate advantage.
In what concerns cognitive abilities, primates usually outrank other mammals of similar, or even larger, brain size, as illustrated by comparisons between a macaque monkey and a capybara; a chimpanzee and a cow; or a human and a dolphin, whale, or elephant. Such a cognitive advantage is inconsistent with the traditional view of brain scaling in mammalian evolution as a homogeneous phenomenon regarding numbers of neurons and neuronal density, with brains of different sizes viewed as similarly scaled-up or scaled-down versions of a shared basic plan. Here, I will argue, instead, that different neuronal scaling rules apply to different mammalian orders and that the particular rules that apply to primates are such that endow us with an advantage over other mammals that is likely to have important cognitive consequences: a larger number of neurons concentrated per volume in the brain.


Hyperocclusion stimulates the expression of collagen type XII in periodontal ligament.
It is known that excessive mechanical force exerted by hyperocclusion induces occlusal trauma. However, the mechanism of the process remains unclear. In the present study, we employed an in vivo hyperocclusion rodent model to examine morphological and biological mechanisms of occlusal trauma in periodontal ligament tissue. To investigate alveolar bone resorption, tooth sections were stained to detect osteoclasts. To investigate the relationship between hyperocclusion and the regeneration of the cell matrix, we examined the effect of hyperocclusal force on the expression of collagens using immunohistochemistry and quantitative PCR methods. The arrangement of collagen fibers in the furcation area of the teeth was undisturbed before hyperocclusion (control). Type I collagen was localized in the extracellular area at the furcation and there was faint expression and localization of type XII collagen in the periodontal ligament. The number of osteoclasts significantly increased in the furcation and lingual cervical regions on day 4 after hyperocclusion was induced. Type XII collagens were gradually up-regulated following the induction of hyperocclusion, in a time-dependent manner. Although type I collagen mRNA expression was stable before and after hyperocclusion, type XII collagen mRNA was significantly up-regulated on day 2 and day 4 after hyperocclusion treatment. Our findings indicate that hyperocclusal force predominantly up-regulates the expression of type XII collagen in periodontal tissue, but not type I collagen, suggesting that there is a mechanism for regeneration of periodontal tissues as a response to occlusal trauma.


Conceptions of Educational Practices Among the Nahuas of Mexico: Past and Present.
Historical documents and recent fieldwork indicate that, since the sixteenth century, there is robust continuity in central beliefs about learning among Nahuatl families. Nahuatl documents from nearly five centuries ago and current Nahuatl adults consider guidance and teaching to be accompaniment of the learner, more than direct action, because nobody can enter the minds and personalities of others. Learning by observing and pitching in is valued: The adults can organize good conditions of apprenticeship, they can indicate the good direction and the goal, serve as examples, and protect the learner. Across centuries, Nahuatl educational practices consist of facilitating observation by copresence, early training for attentive engagement, hiding nothing, and not preventing children from trying, as well as persuading children to be responsible, to work, and to adopt a calm attitude for paying close attention.


Synthesis of a mordenite/ZSM-5/chabazite hydrophilic membrane on a tubular support. Application to the separation of a water-propanol mixture.
A selectivity of 71 is achieved in the separation of a gas phase water-propanol mixture, using a mordenite/ZSM-5/chabazite membrane that is hydrothermally synthesized onto the inner surface of a porous α-alumina tubular support.


[Trophoblastic disease in one ovum in a twin pregnancy].
A case of trophoblastic disease in a twin pregnancy is described from its diagnosis to follow-up after emptying of the uterine cavity. The possible causes of trophoblastic disease are discussed.


Method of data interpretation for the determination of abuse liability in rodent self-administration studies under the FDA guidance document.
All new molecular entities that enter the CNS and exert an activity in the brain must be assessed for abuse liability prior to a New Drug Application approval by the US Food and Drug Administration. One element of the screening process is the assessment of the reinforcing properties of the drug candidate using the regulatory-preferred species, the rat. We describe one method of data review from the standard rat IV SA study design that can be used to conclude the relative abuse liability of the new drug entity. While we do not claim the process as the only way to review or interpret the data, we believe the steps described highlight a process that the pharmaceutical development team can use as a starting point for a discussion during study protocol development.


[Treatment results after primary management of severely dislocated ankle fractures with external fixation and subsequent internal osteosynthesis].
Between 1 January 2001 and 30 June 2003, 31 patients with dislocated ankle fractures were primarily treated with an external fixator in our clinic. The aim of the present study was to investigate whether such a concept would determine the overall outcome or influence single parameters such as mobility, dystrophy, pain, arthritis, and complications. Of the 31 patients, 25 aged 18-84 years at the time of the accident were followed up for 6-23 months to assess range of motion, clinical scores, radiological findings, and complications. An isolated injury was present in 23 patients and 3 were open injuries of second to third degree. Between two and five operations were necessary 4-27 days after trauma. The duration of primary hospital care required ranged from 10 to 43 days. The Olerud and Molander score (9 criteria with 100 max points) was 80 points at the follow-up investigation (rated "good"). "Excellent" results (>90 points) were observed in four cases. In the range of motion there was only an average loss in plantar flexion of 12.4 degrees compared to the healthy side in the patients followed up. The treatment result in the study population was compared to the results of prospective studies investigating dislocated ankle joint fractures as well as with our own random sample (n=7) of patients with secondarily treated ankle joint fractures that were initially treated with a cast. Initial external fixation seems to be justified and leads to acceptable results. The main functional lesions are not correlated to the specific treatment selected.


Scarf osteotomy for hallux valgus surgery: determining indications for an additional Akin osteotomy.
There is a lack of clear indications to carrying out an Akin osteotomy in addition to scarf osteotomy. Recent studies have shown that a proximal distal phalangeal articular angle (PDPAA) of > 8° as an indication to carrying out additional Akin osteotomy correlates with better radiological outcomes with lesser risk of recurrence. Our study aimed to validate carrying out the additional Akin osteotomy at a PDPAA > 8° while looking into functional outcomes which have not been studied. Patients who underwent scarf and combined scarf and Akin osteotomy in our institutional registry was identified. Patient reported outcome measures were compared between patients who underwent scarf and combined scarf and Akin osteotomy. The Visual Analogue Scale (VAS), American Orthopedic Foot and Ankle Score (AOFAS), Short Form-36 Physical Component Score (PCS) and Mental Component Score (MCS) were measured pre-operatively and across a follow up period of 2 years. A total of 212 cases were identified. At a PDPAA > 8, there was no difference in VAS, AOFAS, PCS and MCS between patients that had isolated scarf osteotomy and those that received combined scarf and Akin osteotomy pre-operatively, and at 6 months. However, at 2 years post-operatively, patients that received scarf and Akin osteotomy had a significantly better AOFAS score as compared to patients with isolated scarf osteotomy (82.3 ± 15.3 vs 88.4 ± 13.0, p = 0.0224). On the contrary, at a PDPAA < 8, patients who underwent combined scarf and Akin osteotomy had a significantly lower VAS score at 6 months (1.16 ± 2.16 vs 0.321 ± 1.09, p = 0.00633) and 2 years (0.698 ± 1.73 vs 0.333 ± 1.46, p = 0.0466). They also had a higher AOFAS score at 6 months (80.7 ± 14.3 vs 85.4 ± 12.5, p = 0.0123) and 2 years (83.0 ± 14.0 vs 90.7 ± 9.9, p < 0.0001). PDPAA > 8° can serve as a valid indication to carrying out additional Akin on top of scarf osteotomy based on functional outcomes. However, further studies should investigate a PDPAA threshold that is lower than 8°, which can potentially allow more patients to receive the additional Akin osteotomy that can bring better functional outcomes.


Evolution: Divergent trajectories predate the origins of animals and fungi.
Animals, fungi, and their closest protist relatives comprise the clade Opisthokonta. Although they are comparatively closely related, animals and fungi have diverged greatly from one another. A new study demonstrates that the genomic features that are characteristic of animals and fungi arose even before the origin of these two kingdoms.


Neurochemical correlates of alloxan diabetes: gamma amino butyric acid of amphibian brain.
The levels of gamma aminobutyric acid decreased, while glutamic acid and aspartic acid levels increased in the forebrain, and decreased in the mid and hind brain regions of frog, Rana cyanophlictis during alloxan diabetes. Since glutamic acid and GABA are intimately involved in the central nervous system (CNS) functions, the alterations occurring in their levels during alloxan diabetes may be significant in bringing about a correlation between the diabetic state and the altered functional dynamics of the CNS.


Measuring body weight distribution during sit-to-stand in patients with early knee osteoarthritis.
People with severe degenerative conditions, such as osteoarthritis (OA), have been shown to have altered movement patterns during sit-to-stand. However it remains unclear whether such alterations exist in people with early OA, in the absence of pain. This study aimed to determine if a novel seat could be used to discriminate people with early OA compared with controls. The sit-to-stand task was performed by 20 people with early medial knee OA and 20 age and gender-matched control subjects, using an instrumented seat. OA subjects showed altered weight distribution in the transition phase from sit to stand, in that they placed more load through their unaffected side. Task duration was significantly longer for OA subjects, and ground reaction force integrals were significantly greater for both legs of OA subjects. OA subjects had significantly higher knee flexion and adduction moments in their unaffected compared with affected side. This study has demonstrated that a novel instrumented seat can be used to discriminate people with early medial knee OA during the sit-to-stand activity. These results may be relevant for early interventions to delay or prevent changes in muscle function of the affected limb as well as contralateral knee or hip osteoarthritis in these patients.


Phenotypic changes and cell cycle activation in early tubulointerstitial injury of rat adriamycin nephrosis.
Tubular response, including phenotypic changes against a variety of injuries, is an initial event that promotes tubulointerstitial injuries. Using the progressive kidney disease model of rat adriamycin (ADR) nephrosis, the present study focused on the cell cycle activation and phenotypic changes that occur in the tubuli in early tubulointerstitial injury in ADR nephrosis. At 12 weeks, experimental animals developed overt nephrosis with tubulointerstitial injury, which correlated well with the degree of proteinuria and incidence of glomerulosclerosis. Initial pathology of the tubuli showed a slight dilatation of tubuli, which tended to occur in individual nephrons. Immunohistochemistry demonstrated that vimentin-positive tubuli and osteopontin (OPN)-positive tubuli were associated mostly with proliferating cell nuclear antigen expression. Protein levels of OPN in the renal cortex were correlated with the level of proteinuria by western blotting. Vimentin- and OPN-expressing tubuli were tightly associated with a peritubular influx of alpha-smooth muscle actin (SMA)-positive cells or ED-1-positive cells. In addition, we found thrombomodulin+/ TUNEL+ (dUTP-biotin nick-end labeling) peritubular endothelial cells and ED-1+/alpha-SMA+ cells at an early stage among interstitial inflammatory cells. These results suggest that cell cycle activation in tubular cells forms the background for the phenotypic tubular changes that are involved in chronic tubulointerstitial injury in ADR nephrosis.


[Clinical and microbiological evaluation of hyaluronic acid and chlorhexidine mouthwash in the treatment of peri-implant mucositis].
The aim of this study was to evaluate the effectiveness of hyaluronic acid and chlorhexidine mouthwash in the treatment of peri-implant mucositis. Clinical and microbiological studies were conducted before and 14 days, 1, 3 and 6 months after the periodontal treatment in 46 patients (144 implants with fixed dentures) with peri-implant mucositis. The patients were divided into 3 groups: test, comparison and control. Basic periodontal therapy in all groups included professional cleaning and individual oral hygiene training. Test group (15 patients) received basic periodontal therapy plus 0.20% chlorhexidine with hyaluronic acid mouthwash, the comparison group (15 patients) - basic periodontal therapy +0.05% chlorhexidine mouthwash. In control group (16 patients), treatment was limited to basic periodontal therapy only. At the initial stages of observations, there was a statistically significant improvement in the clinical indices in all treatment groups (p<0.001). The use of 0.20% chlorhexidine with hyaluronic acid mouthwash revealed a higher quality of treatment. After 6 months of observation, the clinical features in patients of the control group was almost similar to the state before treatment. The patients of the test group had a more pronounced elimination of facultative and periodontal pathogens in comparison with other groups. The use of 0.20% chlorhexidine with hyaluronic acid containing mouthwash allows the clinician to achieve a better results in the treatment of peri-implant mucositis. The evaluation the oral microflora in patients with peri-implant mucositis can be used as a prognostic criterion for the outcomes of rehabilitation.


Echocardiography signs of early cardiac impairment in patients with breast cancer and trastuzumab therapy.
Recent studies in breast cancer patients and Trastuzumab therapy (Herceptin) showed a development of a toxic cardiomyopathy as a severe complication. The aim of this study was to discover early changes in cardiac function and morphology. We studied 42 female patients with Her-2/-neu over-expression in breast cancer by echocardiography before, 3, and 6 months after start of the adjuvant Herceptin therapy. All values were mean value ± standard deviation. After 3 or 6 months of a trastuzumab therapy we discovered significant increases in the diastolic and systolic left ventricle volume indices (LV-DVI 32.4 ± 8.5 vs. 38.5 ± 8.7 vs. 40.3 ± 10.3 ml/m², p < 0.001 and LV-SVI 12.6 ± 4.0 vs. 15.7 ± 4.7 vs. 17.2 ± 6.8 ml/m², p < 0.001), an increase of the end-diastolic and end-systolic LV diameter (LVEDD 46.8 ± 4.2 vs. 48.0 ± 4.7 vs. 49.7 ± 4.5 ml/m², p < 0.01; LVESD 28.3 ± 4.2 vs. 31.0 ± 4.7 vs. 32.3 ± 4.9 mm, p < 0.001), a reduced systolic ventricle function determined by the tissue Doppler imaging (TDI) velocity (9.2 ± 2.5 vs. 8.0 ± 1,7 vs. 7.7 ± 1.5 cm/s, p < 0.001), fractional shortening (39,6 ± 7.5 vs. 35.4 ± 7.4 vs. 35.2 ± 7.0%, p < 0.01), and the LV-EF Simpson biplane [62.0 ± 5.1 vs. 60.1 ± 6.3 (p = ns) vs. 58.4 ± 7.9%, p < 0.01] compared to pretreatment values. There was also an increase of the left atrial volume index (21.4 ± 6.2 vs. 26.2 ± 7.9 vs. 29.7 ± 8.8 ml/m², p < 0.001), a decrease of the median TDI atrial velocities (11.9 ± 2.4 vs. 10.5 ± 2.8 vs. 10.1 ± 2.1 cm/s, p < 0.01), an increase of the peak early diastolic filling velocities (73.1 ± 15.4 vs. 83.1 ± 16.4 vs. 82.2 ± 19.4 cm/s, p < 0.05), and an increase of the median mitral valve insufficiency degree (0.64 ± 0.65 vs. 1.03 ± 0.76 vs. 1.11 ± 0.73°, p < 0.001). We could not detect a significant increase in diastolic dysfunction. Also right heart diameters and function did not change significantly. Most patients stayed in an asymptomatic stage of cardiac disease. The blockade of Her2/-neu receptors with trastuzumab in patients with breast cancer led to measurable alterations of left ventricular volume, left atrial volume, and systolic function as early as 3 months after start of treatment.


Outcomes and complications of a modified tibial tuberosity transposition technique in the treatment of medial patellar luxation in dogs.
To report a modification of the tibial tuberosity transposition (m-TTT) technique used to treat medial patellar luxation (MPL) in dogs, and report its complications. Retrospective case series. Dogs (n = 235) undergoing MPL correction, using m-TTT (n = 300 stifles). Medical records and client surveys were reviewed to determine complications associated with this technique and they were compared with previously reported complications using similar techniques. Short-term minor complications included low-grade reluxation (11 stifles, 3.6%), incisional seroma (nine stifles, 3%), pin-associated swelling (seven stifles, 2.3%), patellar desmitis (six stifles, 2%), superficial incisional infection (four stifles, 1.3%), pin migration (three stifles, 1%), tibial tuberosity (TT) fracture (two stifles, 0.6%), tibial tuberosity displacement and patella alta (one stifle, 0.3%), pin-associated discomfort (one stifle, 0.3%), trochlear block fracture (one stifle, 0.3%). Short-term major complications included pin migration (three stifles, 1%), incisional infection (two stifles, 0.6%), tibial tuberosity fracture (two stifles, 0.6%), and high grade reluxation (two stifles, 0.6%). Long-term follow-up examination data were available for 109/300 (36.3%) stifles. One minor complication and four major complications were documented. All long-term complications were due to pin migration. The overall major complication rate was 4.3% (13/300 stifles), with a minor complication rate of 15% (46/300 stifles). The owner survey indicated a 100% satisfaction rate. The m-TTT technique yielded acceptable complication rates, with high owner satisfaction. The m-TTT should be considered as an alternative technique for treating dogs with MPL requiring a tibial tuberosity transposition.


Multilevel regulation of endoplasmic reticulum stress responses in plants: where old roads and new paths meet.
The sessile lifestyle of plants requires them to cope with a multitude of stresses in situ. In response to diverse environmental and intracellular cues, plant cells respond by massive reprogramming of transcription and translation of stress response regulators, many of which rely on endoplasmic reticulum (ER) processing. This increased protein synthesis could exceed the capacity of precise protein quality control, leading to the accumulation of unfolded and/or misfolded proteins that triggers the unfolded protein response (UPR). Such cellular stress responses are multilayered and executed in different cellular compartments. Here, we will discuss the three main branches of UPR signaling in diverse eukaryotic systems, and describe various levels of ER stress response regulation that encompass transcriptional gene regulation by master transcription factors, post-transcriptional activities including cytoplasmic splicing, translational control, and multiple post-translational events such as peptide modifications and cleavage. In addition, we will discuss the roles of plant ER stress sensors in abiotic and biotic stress responses and speculate on the future prospects of engineering these signaling events for heightened stress tolerance.


A modifier mutation affecting utilization of mannitol in pneumococcus.
The altered growth of a pneumococcal mutant containing marker M, which confers ability to utilize mannitol, and a modifier gene is reported. The modifier gene is closely linked to the M gene and imposes a requirement for growth in 0.4% glucose before growth in mannitol medium. The tentative position of the M gene of pneumococcus is ery-r str-r M sul-rd.


High performance tube sensor based on PANI/Eu3+ nanofiber for low-volume NH3 detection.
A novel polyaniline (PANI)/Eu3+ nanofiber sensing film was prepared in the presence of Eu(NO3)3 which serves as structure-directed agent. The morphological, component, crystallinity and electrochemical properties were carried out by using Scanning Electron Microscope (SEM), Energy-Dispersive X-ray (EDX), Fourier Transform Infrared spectroscopy (FT-IR), X-Ray Diffraction (XRD) and Brunauer-Emmett-Teller (BET) techniques. The results indicated the nanofiber-like network with porous structure appeared in the PANI embedded by Eu3+ ions, thereby leading to large specific surface area. Furthermore, the PANI/Eu3+ nanofibers were grown onto the inner wall of capillary glass to form the tube sensor. By the sensing measurements, this tube sensor enabled the detection of low-volume (0.3 mL) NH3 for response 435% at concentration of 0.25 ppm with a short response time (5 s) and recovery time (5 s), and the performances of reproducibility and selectivity were also excellent. The above results demonstrated the potential application of PANI/Eu3+ tube sensor for low-volume NH3 gas.


Sensitization of melanoma cells for death ligand-induced apoptosis by an indirubin derivative--Enhancement of both extrinsic and intrinsic apoptosis pathways.
Until today effective therapies are lacking for metastatic melanoma. The death ligand TRAIL appears as promising in cancer treatment; however, melanoma cells reveal both preexisting and inducible TRAIL resistance. Here, we present evidence that the recently described indirubin derivative 8-Rha-β enhances melanoma cell sensitivity for death ligands and overcomes resistance to TRAIL and CD95 agonists. Indirubin is known from traditional Chinese medicine and is a potent kinase inhibitor. Unraveling of apoptotic signaling pathways revealed that TRAIL resulted in a quick (within 8h) downregulation of both agonistic TRAIL receptors DR4 and DR5, in a kind of negative feed-back loop. Treatment with indirubin, however, mediated upregulation of both receptors, thus compensating this negative feed-back loop by TRAIL. Furthermore, indirubin activated intrinsic apoptosis pathways, seen in loss of mitochondrial membrane potential and release of cytochrome c. The mitochondrial response appeared as related to upregulation of Bax and Bad and to downregulation of Mcl-1. Remarkably, indirubin in combination with TRAIL was also able to overcome apoptosis resistance due to ectopic Bcl-2 overexpression. The tumor suppressor p53 appeared as master regulator of these propapoptotic changes and is the transactivator of proapoptotic proteins which was upregulated by indirubin. Taking into account the physiological role of death ligands in immune surveillance, sensitization of melanoma cells for death ligands may be supportive for an anti-tumor immune response. Furthermore, combinations with kinase inhibitors, such as indirubin 8-Rha-β may help for a breakthrough of TRAIL-mediated strategies in melanoma.


Correction to: Sonographic follow-up after endoscopic carpal tunnel release for severe carpal tunnel syndrome: a one-year neuroanatomical prospective observational study.
An amendment to this paper has been published and can be accessed via the original article.


Synthesis and characterization of hapten-quantum dots bioconjugates: Application to development of a melamine fluorescentimmunoassay.
A general and universal analytical strategy for characterization of hapten-BSA conjugates based on complementary optical spectroscopy and molecular mass spectrometry techniques is here described. The proposed procedure provides highly-valuable information about the molecular weight of the conjugate, its stoichiometry and the concentration of the precursors (hapten and BSA) in the conjugate; such information is of great analytical interest for further development of novel quantitative immunoassays. Further, due to great demand of new, simple and robust methodologies for the melamine analysis in milk infant formula, a new immunoprobe melamine-bovine serum albumin-quantum dot was synthetized, characterized and successfully applied in a competitive fluorescent quantum dot-based immunoassay. It should be highlighted that the limit of detection achieved without any sample pretreatment, 0.15 mg kg(-1) for melamine in milk infant formula, is one order of magnitude lower than the maximum concentration level allowed by international legislation in such type of samples. Finally, this simple approach was validated by the use of an alternative technique (HPLC-UV) for the analysis of melamine in contaminated milk infant formula, showing a good agreement between the results obtained by using both analytical methodologies.


What is the effect of treatment modality on red blood cell distribution width in patients with acute cholecystitis?
The red blood cell distribution width (RDW) has recently been used as a marker to predict outcome in various patient groups. In this study, we aimed to examine how RDW is influenced during the treatment and follow-up of cases of acute cholecystitis which is a common inflammatory disease. Seventy-two patients who were treated for acute cholecystitis, were included into the study. The demographic data, leukocyte count, RDW, C-reactive protein (CRP) values and treatment protocols of these patients were prospectively recorded. The patients who received medical treatment for acute cholecystitis (Group A, n=33) and those who underwent surgery (Group B, n=39) were examined in separate groups. There were 27 male and 45 female patients with a mean age of 50.1±18 years (min-max: 21-94). In Group B, 33 patients underwent laparoscopic cholecystectomy, whereas 6 patients underwent open cholecystectomy. The RDW values on admission were not significantly different between two groups. However the post-treatment/pre-discharge RDW values were significantly lower in the surgical group (14.4±1.9 to 13.6±1.1, respectively, p<0.05). Also, no significant RDW change was identified in the medical treatment group based on an intra-group assessment, whereas a significant decrease was observed in Group B (on admission and following surgical treatment: 14.3±1.3, 13.6±1.1, respectively, p=0.015). No significant differences were observed between groups in terms of CRP and leucocyte values. There was a significant decrease in RDW values in patients who were treated with surgery for acute cholecystitis, while this response could not be observed with medical treatment.


5-Lipoxygenase products regulate basophil functions: 5-Oxo-ETE elicits migration, and leukotriene B(4) induces degranulation.
5-Lipoxygenase (5-LO) products have been strongly implicated in the pathogenesis of allergic diseases. In addition to their physiologic effects on residential cells, 5-LO products are capable of stimulating various eosinophil functions. However, little is known regarding the effects of 5-LO products on basophil functions. This study was designed to elucidate the effects of the main 5-LO products (ie, leukotriene [LT] B(4), LTD(4), and 5-oxo-6,8,11,14-eicosatetraenoic acid [5-oxo-ETE]), as well as their receptor expression on human basophils. We studied the effects of 5-LO products on Ca(2+) mobilization, migration, CD 11b expression, and degranulation of human basophils. Expression of the receptors for LTC(4)/D(4)/E(4) (cysteinyl leukotriene 1 [CysLT(1)] and CysLT(2)), LTB4 (BLT(1) and BLT(2)), and 5-oxo-ETE (oxoeicosanoid [OXE]) was assessed by means of real-time PCR and flow cytometry. At the mRNA level, basophils strongly expressed OXE and predominantly expressed CysLT(1) and BLT(2). The expression level of OXE mRNA in basophils was approximately 20-fold higher than in neutrophils and similar to that in eosinophils. At the protein level, basophils expressed CysLT(1), CysLT(2), BLT(1), and OXE, but not BLT(2). All products elicited a transient increase of cytosolic calcium, with the order of magnitude being LTB(4)>5-oxo-ETE>LTD(4). 5-Oxo-ETE induced a strong basophil migratory response that was almost equivalent to that of prostaglandin D(2). LTB(4) elicited significant degranulation of IL-3-primed basophils. In contrast, no functional significance was observed for LTD(4). Among 5-LO products, 5-oxo-ETE induces a potent basophil migratory response, and LTB(4) elicits degranulation under certain conditions. Our results strongly suggest that 5-oxo-ETE might afford opportunities for therapeutic targeting in allergic inflammation.


[Significance of psychological stress, absence of stress and resources for health promotion at the workplace].
Stress is defined as a lasting, averse situation, the avoidance of which appears to be subjectively important and where the individual is not sure of having enough ability to control it. Eustress, contrary to this, is characterized by the individual's confidence of being able to master given demands successfully. Therefore eustress can not equated with stress. One may assume that the repeated experience of mastering given demands constitutes a resource in coping with stressors. Empirical findings have shown psychic stressors to be systematically linked with individual discomfort preceding clinical symptoms. Therefore alterations to psychic stressors may be a mean of prophylaxis. Data from surveys on blue-collar workers moreover have suggested that two working conditions themselves may provide resources for coping with stressors: decision latitude and social support. Hence enlarging decision latitude and enhancing social support may be possibilities for prevention, especially in such cases, where stressors cannot (yet) be directly changed.


Clinical Relevance of Secreted Small Noncoding RNAs in an Embryo Implantation Potential Prediction at Morula and Blastocyst Development Stages.
Despite the improvements in biotechnological approaches and the selection of controlled ovarian hyperstimulation protocols, the resulting pregnancy rate from in vitro fertilization (IVF) protocols still does not exceed 30-40%. In this connection, there is an acute question of the development of a non-invasive, sensitive, and specific method for assessing the implantation potential of an embryo. A total of 110 subfertile couples were included in the study to undergo the IVF/ICSI program. Obtained embryos for transfer into the uterine cavity of patient cohort 1 (n = 60) and cohort 2 (n = 50) were excellent/good-quality blastocysts, and small noncoding RNA (sncRNA) content in the corresponding spent culture medium samples at the morula stage (n = 43) or at the blastocyst stage (n = 31) was analyzed by deep sequencing followed by qRT-PCR in real time. Two logistic regression models were developed to predict the implantation potential of the embryo with 100% sensitivity and 100% specificity: model 1 at the morula stage, using various combinations of hsa_piR_022258, hsa-let-7i-5p, hsa_piR_000765, hsa_piR_015249, hsa_piR_019122, and hsa_piR_008112, and model 2 at the blastocyst stage, using various combinations of hsa_piR_020497, hsa_piR_008113, hsa-miR-381-3p, hsa_piR_022258, and hsa-let-7a-5p. Protein products of sncRNA potential target genes participate in the selective turnover of proteins through the ubiquitination system and in the organization of the various cell cytoskeleton and nucleoskeleton structures, regulating the activity of the Hippo signaling pathway, which determines the fate specification of the blastomers.


Choosing Sustainability: Decision Making and Sustainable Practice Adoption with Examples from U.S. Great Plains Cattle Grazing Systems.
Sustainable intensification of animal agriculture will rely on the acceptance and adoption of many new practices and technologies. We discuss the literature related to behavior change and sustainable practice adoption in the context of beef cattle production, focusing on sustainable rotational grazing and the use of cover crops. Research from a variety of contexts is discussed with a conceptual framework that combines diffusion of innovation theory with the reasoned action approach. Background characteristics of producers and their operations as well the characteristics of any new practice/technology will influence producer perceptions of them. These background and perceived practice characteristics will influence producer behavioral, normative, and control beliefs regarding the behavior, which will in turn inform attitudes about the behavior and perceptions regarding behavioral norms and the capacity to adopt new behaviors. Factors such as the demographics of beef cattle producers, land tenure, and labor and credit availability, as well as producers' concepts of what it means to be a "good farmer", should inform the conceptualization and development of new practices and technologies to increase the likelihood of their adoption.


Successful lens removal in congenital corneolenticular adhesion (Peters' anomaly).
A 6-month-old infant girl with congenital biomicroscopically visible corneolenticular adhesions underwent bilateral cataract aspiration and secondary capsulectomy resulting in bilaterally corrected visual acuity of 6/18 (20/60) at age 6 years.


Effect of chronic uremia on fructose 2,6-bisphosphate glycolytic and gluconeogenic enzymes in rat liver.
The level of fructose 2,6-bisphosphate and the maximal activities of key gluconeogenic and glycolytic enzymes were determined in the liver of a rat model of chronic uremia and in ad libitum-fed control and pair-fed control animals. Fructose 2,6-bisphosphate was decreased in uremia and its level negatively correlated with the concentration of blood urea nitrogen. The changes in gluconeogenic enzymes in uremic rats were not different from those in the pair-fed controls. However, pyruvate kinase was decreased in uremia when compared to both controls. These studies offer a possible mechanism for the role of the liver in the carbohydrate intolerance of uremia.


Three-dimensional ultrasound biomicroscopy, environmental and conventional scanning electron microscopy investigations of the human zonula ciliaris for numerical modelling of accommodation.
Biomechanical modelling of the accommodation process is a useful tool for studying the mechanism of accommodation and presbyopia and can aid in the development of accommodative lens-replacing materials. Existing biomechanical models, however, use a very simplified zonula structure. The aim of this study was to use three-dimensional ultrasonic imaging and scanning electron microscopy to provide a more detailed, three-dimensional description of the structure of the human zonula to improve the modelling of accommodation. Five human eyes were examined without invasive manipulation using a custom-made three-dimensional ultrasonic imaging technique that allows scanning of features with a spatial resolution of 30 microm. Environmental and conventional scanning electron microscopy (SEM) provided information to complement the ultrasonic images for use in development of a more anatomically correct finite-element model of the zonula structures. These data along with the material properties of the ocular tissue structures were used to construct an advanced geometric model for finite-element simulation of the accommodation process. Images were obtained through three-dimensional ultrabiomicroscopy (3D-UBM) of anatomical features heretofore not directly imagable in their native state. Ciliary processes and zonula structures were clearly separated by both the 3D-UBM and the SEM methods. It was found that fibres inserting on the anterior and posterior lens capsule emerge anteriorly at the ciliary body. Fibres emerging near the pars plana insert on the lens and the ciliary body. No X-shaped crossing fibres were found. Modelling of the accommodation process with both the simple and the more complex geometric models produced refractive power changes comparable with in vivo findings. The 3D-UBM allowed examination of zonula structures in their native state with minimized preparation artefacts. While these data were incorporated into a complex and more anatomically correct finite-element simulation of intraocular features including lens, zonular system and ciliary body it was found that a simplified zonular model is sufficient for the numerical simulation of the accommodation process.


Odon device: a promising tool to facilitate vaginal delivery and increase access to emergency care.
The last innovation in operative vaginal delivery happened centuries ago with the invention of the forceps and the vacuum extractor. The World Health Organization Odon Device Research Group recently published a protocol for a feasibility and safety study for a new device (Odon device) which aims to revolutionize assisted vaginal delivery. This editorial discusses the device and its pathway to global use. Although preliminary results look promising, the rigorous three-phased WHO protocol needs completion before the device can be determined, based on the evidence, to be safe and effective.


Removal process of prion and parvovirus from human platelet lysates used as clinical-grade supplement for ex vivo cell expansion.
Pooled human platelet lysate (HPL) is becoming the new gold standard as supplement for ex vivo cell culture for clinical protocols. However, the risk of pathogen contamination of HPL increases with the platelet pool size. We hypothesized that hollow fiber anion exchange membrane chromatography using QyuSpeed D (QSD) could remove resistant and untested bloodborne pathogens, such as parvoviruses and prions, from HPL-supplemented growth media without substantially affecting their capacity to support ex vivo cell expansion. Frozen or thawed platelet concentrates were serum-converted and centrifuged for obtaining HPL that was added to various growth media (ca. 100 mL), filtered through a 0.6-mL QSD membrane and characterized for proteins, growth factors and chemical composition. Capacity to expand Chinese hamster ovary, periodontal ligament, gingival fibroblast cells and Wharton's jelly mesenchymal stromal cells was studied. Removal of porcine parvovirus (PPV) and of the 263K prion strain of hamster-adapted scrapie was studied by spiking experiments following international guidelines. QSD had minimal impact on HPL-supplemented medium composition in proteins, growth factors and chemical content, nor capacity to expand and differentiate cells. In addition, QSD could remove ≥5.58 log10 [TCID50/mL] and ≥3.72 log10 of PPV and the 263K prion, respectively. QSD hollow fiber chromatography can be used to improve the virus and prion safety of HPL-supplemented media to safely expand cells for clinical protocols. These data bring new perspectives for increasingly safer use of pooled HPL in cell therapy and regenerative medicine applications.


Effects of naloxone and naltrexone on meal patterns of freely-feeding rats.
The effects of naloxone and naltrexone on the night-time meal patterning of freely-feeding male rats were investigated using a Kissileff-type eatometer. Naloxone (5.0 mg/kg) and naltrexone (2.5 mg/kg) reduced intake for two hours after IP injection. This effect resulted from a shortening of duration of meals and an extension of postmeal intervals. Unlike other anorexic agents neither drug affected meal frequency or the eating rate within meals. These particular opioid antagonists therefore appear to produce anorexia by advancing meal termination and extending the inhibition of feeding which follows a meal. These specific changes in the structure of the meal pattern consolidate previous findings and support the hypothesis that naloxone and naltrexone reduce food intake in rats by promoting satiation and prolonging satiety.


Temporal pattern of conduction recurrence during radiofrequency ablation for typical atrial flutter.
Conduction recurrence during radiofrequency (RF) ablation of cavotricuspid isthmus for typical atrial flutter is common. Understanding the temporal pattern of recurrences could help to predict a durable bidirectional block (BDB) and optimize the procedure. We analyzed atrial flutter ablations in 108 consecutive patients (85 males, age 63 +/- 11 years). RF energy was delivered through 8-mm tip or 4-mm cooled-tip catheter. On average, 18 +/- 11 pulses were necessary to achieve BDB. The time to recurrence of conduction after RF cessation was recorded. Early and late conduction recurrences were defined as < or =10 minutes and >10 minutes, respectively. Patients were observed for > or =30 minutes after bidirectional cavotricuspid isthmus (CTI) block was achieved. Conduction did not recur in 46 patients. In 8 cases, no block was achieved. A total of 167 conduction recurrences were recorded in the remaining 54 cases (1-10 per case). Of these, in 53 patients, recurrences were classified as early (98%) and 14 patients had late recurrences (8%). Thirteen patients had both early and late recurrences (24%). All but one late recurrence were preceded by at least one early recurrence. Absence of early recurrence had negative predictive value of 98%, while any early recurrence had positive predictive value of 26% for subsequent late conduction recovery. Incidence of isthmus conduction recurrence rapidly decayed during the waiting period. Absence of conduction recurrence within 10 minutes after first successful RF delivery was highly predictive of persistent BDB.


[Saliva ammonia and urea in the sheep. Effects of alimentary nitrogen additives (author's transl)].
The salivary elimination of ammonia and urea was studied in 4 permanently salivary duct fistulated sheep. Sheep were fed either a regular diet or the same diet with addition of non protein nitrogen (NPN). Individual saliva ammonia levels vary from 34 to 71 microgram N/100 ml. After intra-ruminal dosing with urea (10 g) or ammonia (2 g), the values may rise up to 1000 microgram N/100 ml. Saliva ammonia and blood ammonia changes follow the same direction. Daily saliva urea variations are correlated with feeding behaviour. NPN administration increases saliva urea and blood urea; both concentration curves are parallel.


Draft Genome Sequence of Toluene-Resistant Staphylococcus epidermidis SNUT.
Here, we report draft sequence of the Gram-positive toluene-resistant bacterium Staphylococcus epidermidis SNUT. The draft genome sequence is 2,511,658 bases, with 2,346 protein-coding genes, 57 tRNA-coding genes, and 8 rRNA genes.


Genotype modulates prenatal stress effects on aggression in male and female mice.
Prenatal stress (heat and restraint) significantly increased postpartum aggression (proportion of animals fighting and/or the intensity of the behavior) in C57BL/6J female mice and reduced the behavior in DBA/2J females. For intermale aggression, prenatal stress increased the behavior (intensity of aggression) in C57BL/6J males but did not affect aggressive behavior in DBA/2J animals. Infanticidal behavior (the killing of young) exhibited by male mice was not influenced by prenatal stress in either strain. Relative anogenital distance measurements in neonates at birth did not serve as a reliable predictor of strain variation in prenatal stress effects. Prenatal stress did not influence this measure of prenatal androgen exposure in DBA/2J or C57BL/6J females. For males, prenatal stress elevated relative anogenital distance in C57BL/6J mice and decreased this measure in DBA/2J animals. Prenatal stress effects on aggressive behavior in male and female mice therefore depend upon genotype. Strain-dependent differences may be modulated by differences in endocrine reactivity to prenatal stress/and or differential central neural tissue sensitivity to hormones.


Is the inhibitory effect of progesterone on endometrial prostaglandin F2 alpha production due to an inhibition of protein synthesis?
Progesterone and a high concentration of oestradiol (i) reduced the outputs of prostaglandin (PG) F2 alpha and, to a lesser extent, PGE2 from Day-7 and Day-15 guinea-pig endometrium in culture, but had little or no effect on the output of 6-keto-PGF1 alpha, (ii) prevented the increase in PGH synthase concentrations which normally occur in Day-7 and Day-15 guinea-pig endometrium during culture, and (iii) reduced the synthesis of secreted proteins by Day-15 guinea-pig endometrium in culture. These findings suggest that the inhibitory effect of progesterone and of high concentrations of oestradiol on endometrium PGF2 alpha synthesis is due to an inhibition of the syntheses of proteins involved in PGF2 alpha production.


Increased serum C-reactive protein and decreased urinary aquaporin 2 levels are predictive of the efficacy of tolvaptan in patients with liver cirrhosis.
Water retention, hepatic ascites, and peripheral edema are significant problems in patients with liver cirrhosis (LC). Although furosemide and spironolactone are commonly used as treatment, they are often insufficient to treat hyponatremia and renal insufficiency in patients with LC. Tolvaptan (TVP) could provide an effective treatment alternative. However, predictive factors of a therapeutic response to TVP are unclear. Our aim was to examine clinical predictors of the response to TVP in patients with LC and water retention. Fifty-two patients were treated with TVP, with therapeutic effects judged by a decrease in body weight (≥2 kg) and increase in urinary volume (≥500 mL) within 7 days. Blood biochemical tests were carried out at baseline and post-treatment, including serum soluble CD14 (sCD14) and urinary aquaporin 2 (AQP2) levels. Clinical and laboratory predictive factors of a TVP response were evaluated by univariate and multivariate analyses. The overall response to TVP was 55.8%. On univariate analyses, serum C-reactive protein (CRP) level, the neutrophil-to-lymphocyte ratio, urinary blood urea nitrogen, and urinary AQP2 were predictors of the TVP response, with only serum CRP retained on multivariate analysis. A higher serum sCD14 level was strongly associated with a non-response to TVP. A decrease in urinary AQP2 to undetectable level was associated with a response. Tolvaptan provides a rapid and strong effect to improve water retention in patients with LC. Baseline serum sCD14 and CRP levels are useful predictors of a response to TVP, with a decrease in urinary AQP2 during treatment indicating an early response.


Reduction in total leukocytes in malaria patients compared to febrile controls: A systematic review and meta-analysis.
Leukocyte alterations are a common hematological alteration among malaria patients. This systematic review and meta-analysis aimed to provide data and evidence comparing alterations in total leukocyte counts in malaria patients compared to febrile/healthy subjects at baseline before treatment. A systematic review was conducted by following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement for reporting systematic reviews and meta-analyses. Web of Science (ISI), Scopus, and Medline. All published articles reporting a total leukocyte count of patients infected with malaria, non-malaria (febrile or healthy group) at baseline before treatment before August 27, 2019, were retrieved, and data were extracted by two main reviewers independently. We used a forest plot, heterogeneity test (Cochran's Q), and the degree of heterogeneity (I2) to test whether the included studies were heterogeneous. The quality of the included studies was determined by a quality assessment guide based on the quality assessment tool developed by the Newcastle-Ottawa Scale (NOS). Cochran's Q (Chi-square) and Moran's I2 were used to evaluate heterogeneity. Meta-regression using STATA software was conducted to find the source of heterogeneity. A funnel plot with Egger's test was used to examine the significance of publication bias among the included studies. The mean differences were estimated using a random-effects model. Out of the 2,261 articles screened, 29 articles were included in this systematic review and meta-analysis. The heterogeneity test indicated that there was heterogeneity among the included studies with no publication bias. The meta-analysis demonstrated that the total leukocyte count was significantly lower in patients with malaria (n = 4,619) than in those without malaria (n = 10,056) (Z = 4.0, P-value < 0.00001, mean difference = -1.38, 95% CI = -2.06-(-0.71)). Leukocyte differential alterations, low lymphocyte counts (P-value <0.0001, mean difference = -1.03, 95% CI = -1.53-(-0.53)) and a high NL ratio were found in the malaria group (n = 1,579) compared to the non-malaria group (n = 4,991) (P-value <0.0001, mean difference = 0.6, 95% CI = 0.32-0.88). The subgroup analysis indicated that there was a significantly lower total leukocyte count in the malaria group (n = 3,545) than in the febrile group (n = 8,947) (Z = 1.33, P-value < 0.0001, mean difference = -1.76, 95% CI = -2.56-(-0.96)), but no significant difference was found between the malaria group (n = 1,232) and the healthy group (n = 1,679) (P-value > 0.05). As the specific diagnoses in the febrile groups were not reported in the included studies so that the results of the present study need to be carefully interpreted. This systematic review demonstrated that the total leukocyte count was affected by malarial infection at baseline despite the heterogeneity of the included studies. Future work must aim to understand the treatment-related total leukocyte reduction during follow-up or post-treatment outcomes in malaria-endemic settings.


Intensive Glycemic Control for Diabetic Foot Ulcer Healing: A Multicentric, Randomized, Parallel Arm, Single-Blind, Controlled Study Protocol (INGLOBE Study).
Hyperglycemia impairs healing of diabetic foot ulcer (DFU). But there is no evidence regarding benefit of intensive glucose control for healing of DFU. We plan to conduct a randomized, parallel arm, controlled study to assess the role of intensive glycemic management in comparison to conventional glucose control for healing of DFU. Participants with neuropathic DFU (infected or uninfected) having hemoglobin A1c (HbA1c) >8% and without evidence of osteomyelitis from 7 tertiary care hospitals will be enrolled. They will undergo a 2-week run-in phase for optimization of comorbidities, ulcer debridement, and counseling regarding self-monitoring of blood glucose (SMBG). Subsequently, they will be randomized to "intensive glycemic control" arm defined by glycemic targets of fasting blood glucose (FBG) <130 mg/dL, postprandial BG <180 mg/dL, and HbA1c <8%, with basal-bolus insulin regimen and frequent titration of insulin to achieve glycemic targets. The "conventional" arm will continue on prior treatment (oral antidiabetic drugs) with no titration unless meeting rescue criteria. Ulcer area will be calculated by automated wound assessment device (WoundlyClinial app) weekly for first 4 weeks, and less frequently until the 24th week. Standard treatment for DFU, off-loading, and counseling for foot care will be provided in both arms. The primary outcome measure will be number of wounds closed at 12th and 24th weeks. A multivariate regression analysis will be performed to identify the predictors of wound healing with baseline HbA1c, diabetes duration, wound size, wound duration, and background therapies as independent variable. This study will provide the much needed guidance to set optimum glucose targets in people with DFU.


Nemo-Dependent, ATM-Mediated Signals from RAG DNA Breaks at Igk Feedback Inhibit V κ Recombination to Enforce Igκ Allelic Exclusion.
Monoallelic AgR gene expression underlies specific adaptive immune responses. AgR allelic exclusion is achieved by sequential initiation of V(D)J recombination between alleles and resultant protein from one allele signaling to prevent recombination of the other. The ATM kinase, a regulator of the DNA double-strand break (DSB) response, helps enforce allelic exclusion through undetermined mechanisms. ATM promotes repair of RAG1/RAG2 (RAG) endonuclease-induced DSBs and transduces signals from RAG DSBs during Igk gene rearrangement on one allele to transiently inhibit RAG1 protein expression, Igk accessibility, and RAG cleavage of the other allele. Yet, the relative contributions of ATM functions in DSB repair versus signaling to enforce AgR allelic exclusion remain undetermined. In this study, we demonstrate that inactivation in mouse pre-B cells of the NF-κB essential modulator (Nemo) protein, an effector of ATM signaling, diminishes RAG DSB-triggered repression of Rag1/Rag2 transcription and Igk accessibility but does not result in aberrant repair of RAG DSBs like ATM inactivation. We show that Nemo deficiency increases simultaneous biallelic Igk cleavage in pre-B cells and raises the frequency of B cells expressing Igκ proteins from both alleles. In contrast, the incidence of biallelic Igκ expression is not elevated by inactivation of the SpiC transcriptional repressor, which is induced by RAG DSBs in an ATM-dependent manner and suppresses Igk accessibility. Thus, we conclude that Nemo-dependent, ATM-mediated DNA damage signals enforce Igκ allelic exclusion by orchestrating transient repression of RAG expression and feedback inhibition of additional Igk rearrangements in response to RAG cleavage on one Igk allele.


Quinone and nitrofurantoin redox cycling by recombinant cytochrome b5 reductase.
NADH cytochrome b5 reductase mediates electron transfer from NADH to cytochrome b5 utilizing flavin adenine dinucleotide as a redox cofactor. Reduced cytochrome b5 is an important cofactor in many metabolic reactions including cytochrome P450-mediated xenobiotic metabolism, steroid biosynthesis and fatty acid metabolism, hemoglobin reduction, and methionine and plasmalogen synthesis. Using recombinant human enzyme, we discovered that cytochrome b5 reductase mediates redox cycling of a variety of quinones generating superoxide anion, hydrogen peroxide, and, in the presence of transition metals, hydroxyl radicals. Redox cycling activity was oxygen-dependent and preferentially utilized NADH as a co-substrate; NADH was 5-10 times more active than NADPH in supporting redox cycling. Redox cycling activity was greatest for 9,10-phenanthrenequinone and 1,2-naphthoquinone, followed by 1,4-naphthoquinone and 2-methyl-1,4-naphthoquinone (menadione), nitrofurantoin and 2-hydroxyestradiol. Using menadione as the substrate, quinone redox cycling was found to inhibit reduction of cytochrome b5 by cytochrome b5 reductase, as measured by heme spectral changes in cytochrome b5. Under anaerobic conditions where redox cycling is inhibited, menadione had no effect on the reduction of cytochrome b5. Chemical redox cycling by cytochrome b5 reductase may be important in generating cytotoxic reactive oxygen species in target tissues. This activity, together with the inhibition of cytochrome b5 reduction by redox-active chemicals and consequent deficiencies in available cellular cytochrome b5, are likely to contribute to tissue injury following exposure to quinones and related redox active chemicals.


YesT: a new rhamnogalacturonan acetyl esterase from Bacillus subtilis.
YesT, a putative protein from Bacillus subtilis ATCC 6633 that has been provisionally classified as a rhamnogalacturonan acetyl esterase (RGAE) in CE-12 family, was cloned, expressed in Escherichiacoli Rosetta (DE3), and purified. The enzyme is monomeric with a molecular mass of 37 kDa and presents thermophilic properties similar to RGAE from Aspergillus aculeatus, although YesT is more alkaliphilic. The study of inhibitors confirmed the importance of the His and the nucleophilic Ser for the esterase activity, apart from the Asp from the catalytic triad. This enzyme also presents broad substrate specificity, and is active toward 7-aminocephalosporanic acid, cephalosporin C, p-nitrophenyl acetate, beta-naphthyl acetate, glucose pentaacetate, and acetylated xylan. Moreover, YesT achieves a synergistic effect together with xylanase A toward acetylated xylan. As a member of the SGNH family, it does not adopt the common alpha/beta hydrolase fold. The primary sequence analysis and multiple sequence alignment revealed the lack of a two beta-stranded antiparallel sheet, which results in a clear change in the structure together with the disappearance of one of the three 3(10)-helices presented in RGAE structure. The similarities found in this article among the topological diagrams of RGAE, YesT, and Esterase A from Streptomyces scabies, Platelet-Activating Factor AcetylHydrolase, isoform Ib, alpha subunit [PAF-AH(Ib)alpha(1)], PAF-AH(Ib)alpha(2), the esterase domain from hemagglutinin esterase fusion glycoprotein (HEF1) from Influenza C virus, the thioesterase I (TAP) from E. coli, the hypothetical protein a1r1529 from Nostoc sp., and the hypothetical YxiM precursor that all belong to the SGNH family could indicate a possible divergence of such proteins from a common ancestor.


Seroprevalence of anti-N-methyl-D-aspartate receptor antibodies in women with ovarian teratoma.
Recently antibodies against neuronal receptors have been identified as cause of a new type of encephalitis. The anti-N-methyl-D-aspartate receptor (anti-NMDA-R) encephalitis is the prototype of these disorders. Patients have a high incidence of teratomata. Removal of teratoma is considered the essential treatment of anti-NMDA-R encephalitis. Here, we aimed to investigate whether neurologically asymptomatic individuals suffering from ovarian teratomata may have positive anti-NMDA-R antibodies to be detected by an established assay. Over a time period of 15 months, all patients suffering from ovarian teratomata without neurological symptoms were included in this prospective study. Twenty consecutive patients were pair matched to patients with other benign ovarian disease and healthy controls. Preoperatively, patients had a gynaecological examination, transvaginal ultrasound, neurological examination and determination of anti-NMDA-R antibodies. None of the patients or controls presented with neurological symptoms. All tumours could be removed completely by laparoscopy. Anti-NMDA-R antibodies were absent in the group of patients with teratomata as well as in patients with benign ovarian tumours and healthy controls. Testing for anti-NMDA-R antibodies revealed negative findings in well-characterised patients with ovarian teratomata lacking neurological symptoms. Our data support the current clinical practice that a systematic screening for anti-NMDA-R antibodies in teratoma patients is not indicated.


PLA2G5 regulates transglutaminase activity of human IL-4-activated M2 macrophages through PGE2 generation.
Phospholipases A2 are enzymes that liberate membrane-bound lipids in a tissue and cell-specific fashion. Group V secretory phospholipase A2 is necessary for the development of M2 macrophages and their effector functions in a mouse model of the T-helper-2 allergic airway inflammation. However, the function of group V phospholipase A2 in human M2 activation and T-helper-2 inflammation is ill-defined. Transglutaminase-2, a protein cross-linking enzyme, is a newly identified marker of both human and mouse interleukin-4-activated M2 macrophages and is also found in the lungs of patients with asthma. We report that group V phospholipase A2 and transglutaminase-2 colocalized in macrophages of human nasal polyp tissue obtained from patients with T-helper-2 eosinophilic inflammation, and their coexpression positively correlated with the number of eosinophils in each tissue specimen. We demonstrate that in human monocyte-derived macrophages activated by interleukin-4, group V phospholipase A2 translocated and colocalized with transglutaminase-2 in the cytoplasm and on the membrane of macrophages. Moreover, knocking down group V phospholipase A2 with small interfering ribonucleic acid reduced macrophage transglutaminase activity, whereas mass spectrometry analysis of lipids also showed reduced prostaglandin E2 production. Finally, exogenous prostaglandin E2 restored transglutaminase activity of group V phospholipase A2-small interfering ribonucleic acid-treated macrophages. Thus, our study shows a novel function of group V phospholipase A2 in regulating the transglutaminase activity of human interleukin-4-activated M2 macrophages through prostaglandin E2 generation and suggests that group V phospholipase A2 is a functionally relevant enzyme that may have therapeutic value for the treatment of human T-helper-2 inflammatory disorders.


The interaction of phospholipid membranes with poly(ethylene glycol). Vesicle aggregation and lipid exchange.
(1) The water soluble polymer, poly(ethylene glycol), causes aggregation of sonicated vesicles of dimyristoylphosphatidylcholine in a manner consistent with a steric exclusion mechanism. (2) Poly(ethylene glycol) promotes the exchange of lipids between multilamellar vesicles of dimyristoylphosphatidylcholine and dipalmitoylphosphatidylcholine when the lipids are in the liquid-crystalline state. (3) 31P-NMR studies demonstrate that the bilayer configuration of smectic mesophases of dipalmitoylphosphatidylcholine is substantially maintained in the presence of poly(ethylene glycol).


The effect of individualized patient education, along with emotional support, on the quality of life of breast cancer patients - A pilot study.
This study aimed to determine the effect of individualized patient education along with emotional support on the quality of life (QoL) of breast cancer patients undergoing chemotherapy. It also aimed to determine the intervention's feasibility in the Pakistani context. A quasi-experimental design, with pre- and post-test, in two groups, via time block, was used. The study was conducted at a public hospital in Karachi with a sample of 50 patients; 25 patients each in the intervention and control group. The intervention was delivered over a period of six weeks. It comprised verbal and written patient education, availability of a nurse during patients' chemotherapy administration and over the telephone, and a telephone follow-up of the patients by the nurse. patients' QoL was assessed at baseline and at the sixth week of receiving chemotherapy. Tests indicated a significant improvement in the overall QoL, breast cancer subscale scores, and the physical and emotional well-being of the intervention group, as compared to the control group. The intervention effect size was moderate (0.655) for the QoL. The intervention was found to be effective in improving patients' QoL. However, a larger study, in a multi-center setting, is recommended to ascertain the findings of this pilot study.


[Health promotion--as a change of social systems].
Most prevention concepts are principally based on the goal to change people's behavior, yet consider structural changes as important. Often measures concerning structural changes are planned and realized over people's heads. The concept of health promotion according to the Ottawa Charta postulates the planning and realization of structural changes with the participation of the persons affected by it. Methodical hints and concrete examples of such participative changes of social systems (communities, districts, schools, hospitals, firms etc.) are rare in literature. This article outlines how, with the model of the "Public-Health-Action Cycle", changes in social systems can be participatively planned and realized, with the aim of developing or maintaining healthy social systems. Social systems can only be changed together with the people affected (participation), if these systems are comprehensible. In this way, participative structural changes become a practicable goal in health promotion.


Thyroid Dysfunction Following Management of Non-thyroid Head and Neck Cancers.
Head and neck cancers are one of the commonest malignancies in India. Majority of cases of head and neck malignancy undergo chemoradiation with or without surgery. Thyroid bears the brunt in terms of either excision or the gland tends to get irradiated and fibrosed. In either scenario the functionality of gland is lost leading to hypothyroidism and other clinical manifestations. It tends to get subclinical and goes unnoticed. To identify the occurrence of clinical and subclinical hypothyroidism among head and neck cancer patients receiving radiation to the neck and to justify routine use of thyroid function tests during follow up. It was a prospective non randomized control study of 100 patients of head and neck cancer receiving radiotherapy for duration of 1 year. Thyroid stimulating hormone and T3 and T4 estimations were done at baseline and at 3 and 9 months following radiotherapy. Out of 100 patients, 72 (72%) were males and 28 (28%) were females. All the patients received radiation to the neck to a dose of > 30 Gy. 35 patients received concurrent chemotherapy. 11 patients were found to have subclinical hypothyroidism while 32 patients developed significant clinical hypothyroidism (P value of 0.001). Thus a total of 43 patients developed radiation induced hypothyroidism. 20 of the 32 patients who developed clinical hypothyroidism were in the age group of 41-50 years. 11 of 32 patients who developed clinical hypothyroidism received chemoradiation while rest 21 received radiotherapy alone. Mean period for developing radiation induced hypothyroidism was 4.5 months. Hypothyrodism (clinical or subclinical) is an under recognised morbidity of external radiation to the neck which is seen following a minimum dose of 30 Gy to the neck. Recognising hypothyroidism (clinical or subclinical) early and treating it prevents thyroid dysfunction related complications. Hence, thyroid function tests should be made routine during follow up in all patients undergoing radiotherapy.


The first demonstration that a subset of women with hyperemesis gravidarum has abnormalities in the vestibuloocular reflex pathway.
The vestibular system is a major pathway to nausea and vomiting, and the vestibuloocular reflex (VOR) is a central component; its function can be studied using the vestibular autorotation test (VAT). We hypothesize that women with hyperemesis gravidarum (HG) may have VOR abnormalities. Women with HG were compared with women without HG using the VAT. Horizontal and vertical VOR gains and phases were evaluated at 3 frequency ranges: low (2.0 to 3.5 Hz), medium (greater than 3.5 to 5.0 Hz), and high (greater than 5.0 to 6.0 Hz) during pregnancy and postpartum. Twenty women with HG and 48 unaffected women were evaluated in early pregnancy. Women with HG had higher horizontal gains at all 3 frequency ranges. Horizontal phase differences were also observed at medium frequencies. No VAT differences were noted postpartum. Women experiencing HG had a higher mean VOR horizontal gain and lower horizontal phase when compared with unaffected women.


[Ultrasonics of the liver (and bile ducts). The most significant experiences collected at a district hospital (clinical cases)].
The undoubted advantages deriving from the use of abdominal ultrasonography both in diagnosis and medical or surgical treatment are reported. In particular ultrasonography has proved very helpful in the study of pathologies of the liver and biliary tract, especially in a Rural Hospital, where it is not possible to have recourse to more refined diagnostic techniques.


Green synthesized nickel nanoparticles modified electrode in ionic liquid medium and its application towards determination of biomolecules.
An air and moisture stable ionic liquid 1-ethyl-3-methylimidazolium ethyl sulfate (EMIMES) was used as an electrolyte for electropolymerization of L-cysteine followed by electrodeposition of nickel nanoparticles (NiNP) on paraffin wax impregnated graphite electrode (PIGE). The electrodeposited NiNP modified electrode showed good redox activity and stability in 0.1M KOH solution. The modified electrode has been characterized using Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), field emission scanning electron microscopy (FESEM), energy dispersive X-ray spectroscopy (EDS), electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). The modified electrode was examined for electrocatalytic oxidation of some compounds of biological and clinical importance such as vitamin B6, L-tyrosine, L-tryptophan, vanillin, glucose and hydrogen peroxide by cyclic voltammetry to demonstrate the electrocatalytic activity of the electrodeposited NiNPs.


cDNA cloning, in vitro expression, and biochemical characterization of cholinesterase 1 and cholinesterase 2 from amphioxus--comparison with cholinesterase 1 and cholinesterase 2 produced in vivo.
We have isolated cDNAs coding for the complete amino acid sequences of cholinesterase 1 (ChE1) and cholinesterase 2 (ChE2) from amphioxus. Both ChE transcripts have the characteristics of H-type catalytic subunits, which are inserted in the membrane via an ethanolamine-glycan-phosphatidylinositol anchor. The members of the catalytic triad of ChEs, the three pairs of cysteine residues involved in intrachain disulfide bonding, a cysteine near the carboxy terminal of both sequences, which could mediate interchain disulfide bonding, and 11 of the 14 aromatic amino acids that line the catalytic gorge of AChE are conserved. A remarkable difference between the two enzymes is in the region of the acyl-binding pocket, which plays an important role in determining substrate specificity in cholinesterases. ChE2 contains a sequence that resembles the acyl pocket of invertebrate ChE, while the acyl-binding site of ChE1 is novel. There are also differences between the two enzymes in the peripheral anionic site, which mediates inhibition by certain ligands. In vitro expression in COS-7 cells demonstrates that ChE2 hydrolyzes acetylthiocholine almost exclusively, while ChE1 hydrolyzes both acetylthiocholine and butyrylthiocholine. Both enzymes are inhibited comparably by BW284c51, but ChE1 is considerably more resistant to inhibition by propidium, ethopropazine, and eserine than is ChE2. Velocity sedimentation indicates that ChE1 and ChE2 are present as amphiphilic and nonamphiphilic G2 forms in vivo and in vitro. Another molecular form, which sediments at 17 S, is also present in vivo. Nondenaturing gel electrophoresis in conjunction with digestion by phosphatidylinositol-specific phospholipase C demonstrates that the vast majority of ChE1 and ChE2 is present as ethanolamine-glycan-phosphatidylinositol-anchored G2 forms in vivo. ChE1 also possesses an ethanolamine-glycan-phosphatidylinositol-anchor in vitro; however, ChE2 produced in vitro could not be detected on nondenaturing gels.


Poor prognosis after lower-limb amputation irrespective of diabetes status in patients undergoing hemodialysis.
Diabetes mellitus is one of the most important risk factors for lower-limb amputation in patients undergoing hemodialysis. However, the influence of diabetes mellitus on survival after lower-limb amputation is unknown. Patients who underwent lower-limb amputation since 1996 (amputation group) and those who underwent hemodialysis during 2011-2012 (control group) were included and were followed up until July 2022. There were 70 patients (age: 66.3 ± 8.2 years, 80% male, 77% diabetic) in the amputation group and 328 (age: 67.5 ± 13.5 years, 56% male, 33% diabetic) in the control group. The amputation group showed a poorer prognosis than the control group (hazard ratio [HR]: 2.41, p < 0.001). In the control group, patients with diabetes exhibited poorer survival than those without diabetes (HR: 1.86, p < 0.001). In the amputation group, patients with diabetes exhibited improved survival (HR: 0.47, p = 0.02). Patients undergoing hemodialysis who underwent lower-limb amputation exhibited a poor prognosis, irrespective of diabetes status.


Emergency Neuropharmacology.
Management of acute neurologic disorders in the emergency department is multimodal and may require the use of medications to decrease morbidity and mortality secondary to neurologic injury. Clinicians should form an individualized treatment approach with regard to various patient specific factors. This review article focuses on the pharmacotherapy for common neurologic emergencies that present to the emergency department, including traumatic brain injury, central nervous system infections, status epilepticus, hypertensive emergencies, spinal cord injury, and neurogenic shock.


Detection of specific bacterial enzymes by high contrast metal chelate formation. Part II. Specific detection of Escherichia coli on multipoint-inoculated plates using 8-hydroxyquinoline-beta-D-glucuronide.
The use of 8-hydroxyquinoline-beta-D-glucuronide for the demonstration of beta-glucuronidase activity within the family Enterobacteriaceae has been investigated. The compound has been shown to be an effective substrate for the bacterial enzyme and the Michaelis constant for the association has been determined. A multipoint-inoculated method was employed to test 400 routine clinical isolates including those of urinary and faecal origin. When grown on an agar-based medium containing the substrate together with a ferric salt, glucuronidase-positive organisms were revealed by intense black pigmentation located only in the colony mass. The only organism yielding positive results by this method was Escherichia coli. The shigellae tested were negative by this procedure. Of the total biochemically profiled E. coli organisms 80% were specifically visualised by the method. This contrasts with 97% positively obtained by a fluorescence procedure involving use of 4-methylumbelliferone-beta-D-glucuronide but which also gives positive results with Shigella sonnei. A simple, cost-effective procedure involving use of both techniques for specific detection of E. coli is described.


Effects of antidepressants and cyclooxygenase-2 inhibitor on cytokines and kynurenines in stimulated in vitro blood culture from depressed patients.
Immune activation induces a pro-inflammatory state, which enhances the tryptophan degradation into kynurenine (KYN). The involvement of kynurenines has been shown in patients with major depression. Here, the effects of anti-inflammatory medication and antidepressants on cytokines and tryptophan metabolite changes in blood culture with immune challenge [bacterial mimetic lipopolysaccharide (LPS)] were investigated. A total of 21 depressed patients and 38 matched controls were recruited. Whole blood cultures were stimulated with LPS and drugs were added (celecoxib, venlafaxine, reboxetine, imipramine and fluoxetine). Cytokines and kynurenines were analysed. After stimulation with LPS, the interferon-γ and interleukin (IL)-10 secretions were significantly higher in controls than in patients (p = 0.045, p = 0.032), respectively. Adding imipramine and celecoxib abolished the significance for IL-10. Challenge with LPS induced the kynurenine pathway in each group. Regarding the ratio KYNA/KYN, which indicated how much of KYN formed is further catabolised into the neuroprotective arm, the controls' blood cultures showed a significantly higher ratio (p = 0.045). Stimulation with LPS induced increased production of pro-inflammatory and anti-inflammatory cytokines in both groups, but higher responses in controls. This lower production of cytokine responses in depressed patients indicates that their immune cells are in a refractory phase, induced by a pre-existing pro-inflammatory state. For kynurenines, the whole metabolism was enhanced by LPS; however, an imbalance to neuroprotective metabolites was observed just in control blood. A drug effect could only be shown for imipramine and celecoxib, which were beneficial in terms of re-balancing the immune function but not in re-balancing neuroactive metabolites.


Applications of ultrasound in dentistry.
An ultrasonic descaler working at kHz frequencies is used in dentistry to remove attached deposits from the teeth. Such devices offer many advantages over conventional hand instruments by reducing both the work and time involved in the clinical descaling process. Although it is a recognised clinical instrument, there has been little attempt to standardise its acoustic power output. A parameter which may characterise adequately the acoustic emission from these instruments is the displacement amplitude of the probe tip. Modification of the ultrasonic descaler generator has led to the further use of the instrument in other dental areas. Diagnostic applications of MHz ultrasound is limited by the structure and arrangement of the dental tissues. Therapeutic ultrasound has been used to treat a variety of dentally related ailments, and ultrasonic cleaning baths are used to clean both dental instruments and materials.


de novo design and synthesis of N-benzylanilines as new candidates for VEGFR tyrosine kinase inhibitors.
N-Benzylanilines were designed and synthesized as vascular endothelial growth factor (VEGF)-2 inhibitors using de novo drug design systems based on the X-ray structure of VEGFR-2 kinase domain. Among compounds synthesized, compound showed the most potent inhibitory activity toward VEGFR-2 (KDR) tyrosine kinase and its IC(50) value was 0.57 microM.


Mitochondria as the target of the pro-apoptotic protein Bax.
During apoptosis, engagement of the mitochondrial pathway involves the permeabilization of the outer mitochondrial membrane (OMM), which leads to the release of cytochrome c and other apoptogenic proteins such as Smac/DIABLO, AIF, EndoG, Omi/HtraA2 and DDP/TIMM8a. OMM permeabilization depends on activation, translocation and oligomerization of multidomain Bcl-2 family proteins such as Bax or Bak. Factors involved in Bax conformational change and the function(s) of the distinct domains controlling the addressing and the insertion of Bax into mitochondria are described in this review. We also discuss our current knowledge on Bax oligomerization and on the molecular mechanisms underlying the different models accounting for OMM permeabilization during apoptosis.


Effects Of treadmill training on hindlimb muscles of spinal cord-injured mice.
Treadmill training is known to prevent muscle atrophy after spinal cord injury (SCI), but the training duration required to optimize recovery has not been investigated. Hemisected mice were randomized to 3, 6, or 9 weeks of training or no training. Muscle fiber type composition and fiber cross-sectional area (CSA) of medial gastrocnemius (MG), soleus (SOL), and tibialis anterior (TA) were assessed using ATPase histochemistry. Muscle fiber type composition of SCI animals did not change with training. However, 9 weeks of training increased the CSA of type IIB and IIX fibers in TA and MG muscles. Nine weeks of training after incomplete SCI was effective in preventing atrophy of fast-twitch muscles, but there were limited effects on slow-twitch muscles and muscle fiber type composition. These data provide important evidence of the benefits of exercising paralyzed limbs after SCI. Muscle Nerve, 2016 Muscle Nerve 55: 232-242, 2017.


Uric acid to high-density lipoprotein cholesterol ratio predicts cardiovascular mortality in patients on peritoneal dialysis.
Serum uric acid (UA) and high-density lipoprotein cholesterol (HDL-C) disorders are both considered as risk factors of cardiovascular mortality. The predictive value of UA to HDL-C ratio (UHR) has been validated in diabetes. However, association of UHR with cardiovascular (CV) mortality is undetermined in peritoneal dialysis (PD) patients. In this retrospective cohort study, we enrolled 1953 eligible incident patients who commenced PD treatment on our hospital from January 1, 2006 to December 31, 2015, and followed up until December 31, 2019. Of the participants, 14.9% were older than 65 years (mean age 47.3 ± 15.2 years), 24.6% were diabetics, and 59.4% were male. Patients were categorized into quartiles according to baseline UHR level. Multivariate Cox Proportional Regression analysis was applied to explore the association of UHR with mortality. Overall, 567 patients died during a median follow-up period of 61.3 months, of which 274 (48.3%) were attributed to CV death. The mean baseline UHR was 16.4 ± 6.7%. Compared to quartile 2 UHR, hazard ratios (HRs) for the highest quartile UHR were 1.35 (95% confidence interval [CI] 1.06-1.78; P = 0.017) and 1.46 (95% CI 1.00-2.12; P = 0.047) for all-cause and CV mortality, respectively. Subgroup analysis showed that association of UHR with CV mortality was remarkable among PD patients with age ≥65 years, malnutrition (albumin <35 g/L), diabetes, and CVD history. An elevated UHR predicted increased risk of all-cause and CV mortality in PD patients.


A Comprehensive Commentary on the Multilocular Cystic Renal Neoplasm of Low Malignant Potential: A Urologist's Perspective.
Multilocular cystic renal neoplasm of low malignant potential (MCRNLMP) is a cystic renal tumor with indolent clinical behavior. In most of cases, it is an incidental finding during the examination of other health issues. The true incidence rate is estimated to be between 1.5% and 4% of all RCCs. These lesions are classified according to the Bosniak classification as Bosniak category III. There is a wide spectrum of diagnostic tools that can be utilized in the identification of this tumor, such as computed tomography (CT), magnetic resonance (MRI) or contrast-enhanced ultrasonography (CEUS). Management choices of these lesions range from conservative approaches, such as clinical follow-up, to surgery. Minimally invasive techniques (i.e., robotic surgery and laparoscopy) are preferred, with an emphasis on nephron sparing surgery, if clinically feasible.