Histopathological investigation of the 1p/19q-codeleted gliomas resected following alkylating agent chemotherapy.
Lower grade gliomas with 1p/19q codeletion are often responsive to chemotherapy, and several of these have been treated using upfront chemotherapy and subsequent resection following tumor volume decrease. This study aimed to elucidate the histological changes and the mechanism of recurrence after alkylating agent chemotherapy in 1p/19-codeleted gliomas. Fourteen 1p/19q-codeleted gliomas resected following tumor volume decrease after alkylating agent chemotherapy were included and compared with their pre-chemotherapy specimens. Histological changes were investigated using hematoxylin-eosin staining, and changes in proliferative activity, status of glioma stem cells (GSCs), and tumor-infiltrating macrophages were assessed using immunohistochemistry for Ki-67/MIB-1, CD68 as a pan-macrophage/monocyte marker, CD163 as a presumed marker of M2 polarity, and nestin and CD133 as markers of GSCs. The most frequent histological findings following chemotherapy included a sparse glial background and abundant foamy cell infiltration. The Ki-67/MIB-1 index decreased and the number of CD68 + cells increased after chemotherapy. The increasing rate of CD68 + cells in the post-/pre-chemotherapy specimens was inversely correlated with patient prognosis but not tumor response. The number of CD163 + cells, M2/M1 + M2 ratio, and the ratio of GSCs to total tumor cells increased after chemotherapy, and those in the post-chemotherapy specimens were negatively correlated with patient prognosis. There was a correlation between the M2/M1 + M2 ratio and the ratio of GSCs in both pre- and post-chemotherapy specimens. GSCs in conjunction with M2 macrophages constitute the mechanism of resistance to and recurrence after alkylating agent chemotherapy in 1p/19q-codeleted gliomas.


Hyperpolarised 129Xe magnetic resonance imaging to monitor treatment response in children with cystic fibrosis.
Pulmonary magnetic resonance imaging using hyperpolarised 129Xe gas (XeMRI) can quantify ventilation inhomogeneity by measuring the percentage of unventilated lung volume (ventilation defect per cent (VDP)). While previous studies have demonstrated its sensitivity for detecting early cystic fibrosis (CF) lung disease, the utility of XeMRI to monitor response to therapy in CF is unknown. The aim of this study was to assess the ability of XeMRI to capture treatment response in paediatric CF patients undergoing inpatient antibiotic treatment for a pulmonary exacerbation.15 CF patients aged 8-18 years underwent XeMRI, spirometry, plethysmography and multiple-breath nitrogen washout at the beginning and end of inpatient treatment of a pulmonary exacerbation. VDP was calculated from XeMRI images obtained during a static breath hold using semi-automated k-means clustering and linear binning approaches.XeMRI was well tolerated. VDP, lung clearance index and the forced expiratory volume in 1 s all improved with treatment; however, response was not uniform in individual patients. Of all outcome measures, VDP showed the largest relative improvement (-42.1%, 95% CI -52.1--31.9%, p<0.0001).These data support further investigation of XeMRI as a tool to capture treatment response in CF lung disease.


Integrating systematic pharmacology-based strategy and experimental validation to explore mechanism of Tripterygium glycoside on cholangiocyte-related liver injury.
Tripterygium glycoside (TG) is widely used in clinical practice for its multiple bioactivities including anti-inflammatory and immunosuppressive effects. However, emerging studies have frequently reported TG-induced adverse reactions to multiple organs, especially liver. Here, this study aimed to investigate the mechanism of liver damage induced by TG and explore representative components to reflect TG hepatotoxicity. Network pharmacology was used to determine the potential targets of bile duct injury caused by TG. Next, the hepatotoxic effects of TG, triptolide (TP) and celastrol (CEL) were investigated and compared in vivo and in vitro. Liver function was determined by measuring serum transaminase and histopathology staining. The cell proliferation and apoptosis were determined by cell viability assay, scratch assay and flow cytometry. The expression of gene of interest was determined by qPCR and Western blot. Based on the network pharmacological analysis of 12 bioactive ingredients found in TG, a total of 35 targets and 15 pathways related to bile duct injury were obtained. Both TG and TP resulted in cholangiocyte damage and liver injury, as illustrated by increased levels of serum transaminase and oxidative stress, stimulated portal edema and lymphocytic infiltration and decreased expression of cholangiocyte marker, cytoskeletal 19. In addition, TG and TP inhibited cell proliferation and migration, arrested cell cycle and promoted Caspase-dependent apoptosis of cholangiocytes via suppressing the phosphorylation of extracellular regulated protein kinases 1/2 (ERK1/2) and protein kinase B (AKT). While, CEL at equivalent dosage had no obvious hepatotoxicity. We revealed that TG-stimulated liver injury was specifically characterized by cholangiocyte damage and TP might be the decisive ingredient to reflect TG hepatotoxicity. Our results not only provide novel insights into the mechanism underlying the hepatotoxicity effects of TG but also offer reference for clinical rational use of TG.


One Health: embedding it into your work.
The concept of One Health recognises that the health and wellbeing of people, animals, and the environment are inextricably linked, and that, as the world's population grows, professionals across each of these areas must collaborate in order to effect change. Here, Georgina Mills discusses a new action report from the BVA, which focuses on how One Health can work in the real world.


Comparison of remifentanil and fentanyl for postoperative pain control after abdominal hysterectomy.
In this randomized, double-blind study, we investigated the analgesic efficacy and side effects of continuous constant-dose infusions of remifentanil after total abdominal hysterectomy and compared it to fentanyl. Fifty-six adult female patients scheduled for elective total abdominal hysterectomy were enrolled in this study. Patients were randomly assigned to two groups according to fentanyl (group F, n=28) or remifentanil (group R, n=28) for postoperative analgesia. Patients in group F were given fentanyl intravenously with an infusion rate of fentanyl 0.5 microg/kg/hr; group R was given remifentanil with an infusion rate of remifentanil 0.05 microg/kg/min for 2 days. Pain intensity at rest, occurrence of postoperative nausea and vomiting (PONV), dizziness, pruritus, and respiratory depression were assessed 1 hr after arrival at the post-anesthesia care unit, at 6; 12; 24; and 48 hr post-operation and 6 hr post-infusion of the study drug. Pain was evaluated by using visual analogue scale (VAS; 0-10). The time that patients first requested analgesics was recorded as well as additional analgesics and antiemetics. There were no significant differences in VAS, time to first postoperative analgesics, and additional analgesics between the 2 groups. The incidences and severities of PONV and opioid related side effects were not different between the groups; however, there were 3 episodes (10.7%) of serious respiratory depression in group R. Continuous infusion technique of remifentanil did not reveal any benefits compared to fentanyl. Furthermore, it is not safe for postoperative analgesia in the general ward.


Traffic pathways of Plasmodium vivax antigens during intraerythrocytic parasite development.
We investigated the secretory traffic of a Plasmodium vivax antigen (Pv-148) synthesised by the parasite during the blood cycle, exported into the host cell cytosol and then transported to the surface membrane of the infected erythrocyte. Studies of the ultrastructure of erythrocytes infected with P. vivax showed that intracellular schizogony is accompanied by the generation of parasite-induced membrane profiles in the erythrocyte cytoplasm. These structures are detectable soon after the parasite invades the erythrocyte and develop an elaborate organisation, leading to a tubovesicular membrane (TVM) network, in erythrocytes infected with mature trophozoites. Interestingly, the clefts formed stacked, flattened cisternae resembling a classical Golgi apparatus. The TVM network stained with the fluorescent Golgi marker Bodipy-ceramide. Specific immunolabelling showed that Pv-148 was transferred from the parasite to the erythrocyte surface membrane via the clefts and the TVM network. These findings suggest that the TVM network is part of the secretory pathways involved in parasite protein transport across the Plasmodium-infected erythrocyte and that Pv- 148 may represent a marker that links the parasite with the host cell cytoplasm and, in turn, with the extracellular milieu.


Retrospective Review of Surgical Site Infections after Endoscopic Endonasal Sellar and Parasellar Surgery: Multicenter Quality Data from the North American Skull Base Society.
Introduction Transnasal access to the anterior skull base provides a minimally invasive approach for sellar and parasellar masses compared with its open counterparts. The unique microbiome of the sinonasal mucosa provides distinct challenges not encountered with other cranial approaches. The use of antibiotics in these cases has not been standardized, and data remain scarce regarding infectious outcomes. Methods We conducted a multicenter retrospective analysis of shared quality data points for the endoscopic endonasal approach (EEA) for pituitary adenomas, along with other sellar and parasellar region masses that were included by participating institutions. Patient and operative characteristics, perioperative and postoperative antibiotic regimens and their durations, intraoperative and postoperative cerebrospinal fluid leak, and onset of postoperative meningitis and sinusitis were compared. Results Fifteen institutions participated and provided 6 consecutive months' worth of case data. Five hundred ninety-three cases were included in the study, of which 564 were pituitary adenomectomies. The incidences of postoperative meningitis and sinusitis were low (0.67 and 2.87% for all pathologies, respectively; 0.35% meningitis for pituitary adenomas) and did not correlate with any specific antibiotic regimen. Immunocompromised status posed an increased odds of meningitis in pituitary adenomectomies (28.6, 95% confidence interval [1.72-474.4]). Conclusions The results show no clear benefit to postoperative antimicrobial use in EEA, with further larger studies needed.


Separation of thiol and cyanide hydrolysis products of chemical warfare agents by capillary electrophoresis.
The fluorescence derivatizing agent, o-phthalaldehyde (OPA), has been applied to the separation and detection of cyanide and several structurally similar thiols by capillary electrophoresis (CE)-laser induced fluorescence (LIF). Of particular interest to this investigation was the separation of 2-dimethylaminoethanethiol, 2-diethylaminoethanethiol, and cyanide, each of which are hydrolysis products or hydrolysis product simulants of the chemical warfare (CW) agents O-ethyl S-2-diisopropylaminoethyl methylphosphonothiolate (VX), O-isobutyl S-2-diethylaminoethyl methylphosphonothiolate (R-VX), and tabun (GA). Other structurally similar thiols simultaneously resolved by this method include 1-pentanethiol and 2-mercaptoethanol. Instrumental parameters were probed and optimum values for capillary length (50 cm) and inner diameter (75 microm), injection time (30 s) and field strength (15 kV) were determined. Sample stacking methods enabled detection limits of 9.3 microg/L for cyanide, 1.8 microg/L for 2-diethylaminoethanethiol, 35 microg/L for 2-dimethylaminoethanethiol, 15 microg/L for 2-mercaptoethanol, and 89 microg/L for 1-pentanethiol. The linearity of the method was verified over an order of magnitude and the reproducibility was found to be 3.0%.


Influence of structural reinforcements on the twist-to-bend ratio of plant axes: a case study on Carex pendula.
During biological evolution, plants have developed a wide variety of body plans and concepts that enable them to adapt to changing environmental conditions. The trade-off between flexural and torsional rigidity is an important example of sometimes conflicting mechanical requirements, the adaptation to which can be quantified by the dimensionless twist-to-bend ratio. Our study considers the triangular flower stalk of Carex pendula, which shows the highest twist-to-bend ratios ever measured for herbaceous plant axes. For an in-depth understanding of this peak value, we have developed geometric models reflecting the 2D setting of triangular cross-sections comprised of a parenchymatous matrix with vascular bundles surrounded by an epidermis. We analysed the mathematical models (using finite elements) to measure the effect of either reinforcements of the epidermal tissue or fibre reinforcements such as collenchyma and sclerenchyma on the twist-to-bend ratio. The change from an epidermis to a covering tissue of corky periderm increases both the flexural and the torsional rigidity and decreases the twist-to-bend ratio. Furthermore, additional individual fibre reinforcement strands located in the periphery of the cross-section and embedded in a parenchymatous ground tissue lead to a strong increase of the flexural and a weaker increase of the torsional rigidity and thus resulted in a marked increase of the twist-to-bend ratio. Within the developed model, a reinforcement by 49 sclerenchyma fibre strands or 24 collenchyma fibre strands is optimal in order to achieve high twist-to-bend ratios. Dependent on the mechanical quality of the fibres, the twist-to-bend ratio of collenchyma-reinforced axes is noticeably smaller, with collenchyma having an elastic modulus that is approximately 20 times smaller than that of sclerenchyma. Based on our mathematical models, we can thus draw conclusions regarding the influence of mechanical requirements on the development of plant axis geometry, in particular the placement of reinforcements.


Separation of newly formed bone from older compact bone reveals clear compositional differences in bone matrix.
In long bone diaphyses, woven bone forms first and then transitions into a more mineralized compact bone tissue. Prior evidence suggests that the non-collagenous protein composition of woven bone may be distinct from that of more mature bone tissue, particularly with respect to a diverse group of phosphorylated, extracellular matrix proteins. To critically test this hypothesis, we developed an in situ approach to isolate newly formed bone from more mature bone within the same long bone, and combine this anatomical approach with Western blotting to make relative comparisons of 7 phosphorylated matrix proteins important for bone physiology and biomineralization. Interestingly, 75 kDa bone sialoprotein (BSP), 63 kDa osteopontin, and the 75 kDa form of bone acidic glycoprotein-75 (BAG-75) were enriched in primary bone as opposed to more mature cortical bone, while osteonectin, fetuin A, matrix extracellular phosphoglycoprotein (MEPE) and dentin matrix protein-1 (DMP-1) appeared to be equally distributed between these two bone tissue compartments. Analyses also revealed the presence of larger sized forms of osteopontin (and to a lesser degree BSP) mostly in newly formed bone, while larger forms of BAG-75 were mostly detected in more mature cortical bone. Smaller sized forms of DMP-1 and BAG-75 were detected in both newly formed and more mature bone tissue extracts, and they are likely the result of proteolytic processing in vivo. Intact DMP-1 (97 kDa) was only detected in unmineralized matrix extracts. These findings indicate that newly formed bone exhibits a non-collagenous matrix protein composition distinct from that of more mature compact bone even within the same long bone, and suggest that the temporal fate of individual non-collagenous proteins is variable in growing bone.


Ultrasound elastography for the differential diagnosis of nipple retraction.
Nipple retraction is difficult to diagnose radiologically and extremely worrisome for patients. It occurs most commonly due to pathologies such as previous mastitis or an infiltrative malignancy. With this in mind, the goal of this study was to differentiate benign from malignant lesions of nipple retraction, using the differential characteristics of retroareolar area stiffness, observed by means of the new technological modality of ultrasound elastography (USE). Nineteen unilateral nipple retraction cases, including five cases of mammary ductal carcinoma posteriorly infiltrated the areola, two cases of Paget disease, and 12 cases of mastitis, were investigated. Imaging findings [gray-scale ultrasound (US) and USE analyses of the breasts' nipple-areolar complex], pathological evaluation, and the results of 4 years of follow-up treatment were obtained. The recorded images were evaluated by two different radiologists, and all data were analyzed statistically. Statistical analysis showed that there was a strong correlation between the two radiologists' evaluations. The US images were not diagnostic for either the malignant or benign conditions. The correlation between the diagnosis using US and the final diagnosis was calculated as 0.436 (p = 0.006). However, the USE images were more informative since the correlation ratio between the USE results and the final diagnosis was found to be 0.723 (p < 0.001). While the area under the concentration curve (AUC) values that were used for the diagnostic determination of the US results were inconclusive at 0.274 (p < 0.021), the AUC values for USE were significant, with a diagnostic value of 0.866 for all cases (p < 0.01). The USE modality, which is not commonly used in routine practice, has the potential to solve the problem of differentiation of nipple retraction etiologies in the near future.


[Long-term consequences of the effect of ionizing radiation of different LET. Relation of changes in the intensity of light scattering by blood lymphocytes in the early postradiation stages to the prolongation of the life of rats].
Optic properties of rat blood were studied 24 h following gamma- or gamma-neutron-irradiation with different doses. A comparative analysis of the changes observed was performed in relation to life span of animals. It is concluded that remote effects of radiation can be prognosticated by changes in light scattering of the peripheral blood lymphocytes 24 h following irradiation.


Is dynamic arterial elastance a predictor of an increase in blood pressure after fluid administration in pediatric patients with hypotension? Reanalysis of prospective observational studies.
Dynamic arterial elastance (Eadyn ) has been proposed to predict an increase in mean arterial pressure (MAP) after volume expansion in hypotensive adults. We aimed to evaluate the clinical usefulness of Eadyn as a predictor of arterial pressure response after fluid loading in pediatric patients with hypotension. We re-analyzed data of 63 hypotensive children (age, ≤5 years), collected from three previous prospective observational studies about fluid responsiveness. Pulse pressure variation (PPV), stroke volume variation (SVV), and respiratory variation in aortic blood flow velocity (ΔVpeak) were used to calculate Eadyn (PPV/SVV) and modified Eadyn (PPV/ΔVpeak). Preload-dependent patients were defined as those with ΔVpeak ≥12% before fluid loading. Patients were classified as pressure responders, if their MAP increased ≥15% after fluid administration. Mean Eadyn (SD) was 1.06 (0.47) in pressure responders (n=39) and 0.99 (0.48) in nonresponders (n = 24) (mean difference, 0.08; 95% confidence interval [CI], -0.19-0.34; P = .567). Additionally, mean modified Eadyn was 1.27 (0.64) in responders and 1.11 (0.43) in nonresponders (mean difference, 0.17; 95% CI, -0.13-0.46; P = 0.269). Both Eadyn (AUC 0.506; 95% confidence interval [CI], 0.337 to 0.675; P = 0.948) and modified Eadyn (AUC 0.498; 95% CI, 0.328-0.669; P = 0.983), as well as other dynamic variables, could not predict pressure responsiveness in children. Sub-group analysis revealed similar findings in both in 39 preload-dependent and hypotensive patients (26 pressure responders and 13 nonpressure responders). Both Eadyn and modified Eadyn cannot predict whether blood pressure increases with fluid administration in pediatric patients with hypotension.


MiR-223 regulates autophagy associated with cisplatin resistance by targeting FBXW7 in human non-small cell lung cancer.
Cisplatin is widely used as a first-line treatment for non-small cell lung cancer (NSCLC), but chemoresistance remains a major clinical obstacle for efficient use. As a microRNA, miR-223 was reported to promote the doxorubicin resistance of NSCLC. However, whether miR-223 is also involved in cisplatin resistance of NSCLC and the mechanism miR-223 involved in drug resistance is unclear. Accumulated evidence has shown that abnormal autophagy is associated with tumor chemoresistance. The study aimed to study the role of miR-223 on cisplatin sensitivity in NSCLC and uncover the potential mechanisms. NSCLC cells transfected with mimic or inhibitor for miR-223 was assayed for chemoresistance in vitro. MiR-223 expression was assessed by quantitative real-time PCR (qRT-PCR). Western blot were used to study the expression level of F-box/WD repeat-containing protein 7 (FBXW7) and autophagy-related protein. The effect of miR-223 on cisplatin sensitivity was examined by using CCK-8, EdU assays and Autophagic flux assay. Luciferase assays, EdU assays and small interfering RNA were performed to identify the targets of miR-223 and the mechanism by which it promotes treatment resistance. Xenograft models were established to investigate the effect of mir-223 on cisplatin sensitivity. In the present study, we found that the level of miR-223 was significantly positively correlated with cisplatin resistance. MiR-223 overexpression made NSCLC cells resistant to cisplatin treatment. We further found that autophagy mediated miR-223-mediated cisplatin resistance in NSCLC cells. Further mechanistic research demonstrated that miR-223 directly targeted FBXW7. The overexpression of miR-223 could inhibit the level of FBXW7 protein expression, thus promoting autophagy and making NSCLC cells resistant to cisplatin. Finally, we confirmed the increased effect of cisplatin sensitivity by miR-223 Antagomir in xenograft models of NSCLC. Our results demonstrate that miR-223 could enhance autophagy by targeting FBXW7 in NSCLC cells. Inhibition of autophagy by miR-223 knockdown provides a novel treatment strategy to alleviate cisplatin resistance in NSCLC.


Amyopathic Dermatomyositis: A Concise Review of Clinical Manifestations and Associated Malignancies.
Amyopathic dermatomyositis is a rare, idiopathic, connective tissue disease that presents with dermatologic lesions of classic dermatomyositis but lacks the myopathy of this disease. Cutaneous manifestations may include Gottron's sign, heliotrope rash, and characteristic patterns of poikiloderma. There is a substantial risk for developing interstitial lung disease or malignancy in patients with amyopathic dermatomyositis. A literature review of amyopathic dermatomyositis was performed using the PubMed medical database. The key features of amyopathic dermatomyositis, including autoantibodies, clinical presentation and dermatologic manifestations, epidemiology, history, associated malignancies, management, and pathogenesis, are summarized in this review. Cancer (solid tumor) (73/79, 89 %) and hematologic malignancies (9/79, 11 %) were reported in 79 patients, with three patients having more than one malignancy. In addition, there were six patients with amyopathic dermatomyositis who had tumor of unknown primary, and eight patients with cancer-associated amyopathic dermatomyositis for whom no additional details were provided. From the group of 73 tumors for whom primary origin and sex were available, malignancy of the genitourinary organs (24/73, 33 %), aerorespiratory organs (15/73, 21 %), and breast (14/73, 19 %) were the most commonly observed solid organ tumors. Tumors of the genitourinary organs (15/48, 31 %) and breast (14/48, 29 %) were the most frequent neoplasms in women, accounting for 29 of 48 (60 %) cancers, with the most common sites being breast (14/48, 29 %), ovary (8/48, 17 %), and cervix or uterus (5/48, 10 %). In men, tumors of the aerorespiratory (9/25, 36 %) and genitourinary (9/25, 36 %) tracts were the most common neoplasms, accounting for 72 % (18/25) of cancers; the most common sites of primary malignancy were nasopharyngeal (6/25, 24 %), bladder (4/25, 16 %), and either colorectal, lung or prostate cancer (three cancers each, 12 %). In summary, the search for an undiagnosed associated malignancy in patients with amyopathic dermatomyositis should focus towards the organs most frequently affected. Similar to classic dermatomyositis, ovarian and nasopharyngeal cancers are also common in amyopathic dermatomyositis. However, in contrast to lung cancer, which is the most frequent malignancy associated with classic dermatomyositis, breast cancer was the most common type of malignancy reported in patients with amyopathic dermatomyosotis.


Studies on the quantitative structure-activity relationships in pyrazine carbothioamide derivatives.
Quantitative relationships were studied between tuberculostatic potency in vitro and structure parameters of pyrazine carbothioamides. The activity of the compounds was found to be dependent on the parameters related both to the size of the substituent and electronic properties of the molecule. An equation was obtained, statistically significant on the 99% level, which described about 71% of variance of activity data for the compounds under study as a function of molar refractivity of the substituent and the wave length at which absorption maximum occured.


Hepatitis D virus antibody in HBsAg-positive and HBsAg-negative substance abusers with chronic liver disease.
The hepatitis D virus (HDV; previously called the "delta agent") is a defective organism which can replicate only in the presence of the hepatitis B virus (HBV). We tested the serum of 95 substance abusers, all of whom had sufficient evidence of chronic liver disease to warrant a liver biopsy, for hepatitis D virus antibody (anti-HDV). Anti-HDV was detected in five of eight hepatitis B surface antigen (HBsAg)-positive patients and 12 of 87 (14%) HBsAg-negative patients. Antibody to the hepatitis B core antigen (anti-HBc) was the sole hepatitis B marker in eight of the 12 (67%) anti-HDV-positive, HBsAg-negative patients but in only 14 of 75 (19%) anti-HDV-negative, HBsAg-negative patients (P less than 0.005). None of the anti-HDV-positive, HBsAg-negative patients had detectable IgM anti-HBc in the serum or hepatitis D antigen in liver tissue, and they had similar clinical features and liver biopsy diagnoses to HBsAg-negative patients without anti-HDV. We conclude that anti-HDV in HBsAg-negative substance abusers reflects infection with HDV and HBV in the distant past and does not indicate more severe liver disease than that seen in HBsAg-negative patients without anti-HDV.


Advantages and disadvantages in the therapy with different types of interferon for chronic hepatitis C in the elderly patient.
HCV-related hepatitis is a pathology on the increase, and it is especially affecting patients above 60 years old. The only treatment for this disease is therapy with different types of interferon. In this paper the authors compare two of their experiences relative to the treatment of HCV-related chronic hepatitis in the elderly using two types of interferon: recombinant interferon alpha and interferon beta, in order to evaluate their efficacy and side effects. The authors studied and compared two groups of elderly patients from Sicily and Calabria receiving medical care in the department of Geriatrics of the University of Catania. The first group consisted of 20 patients with an age ranging between 60 and 69 years, treated with recombinant interferon alpha; the second group consisted of 26 patients aged between 60 and 75 years treated with interferon beta. After an evaluation of the results, the authors argue that recombinant interferon alpha is preferable since the remission percentage is higher (75%). However, the interferon beta therapy proves to be almost without side-effects. Finally, the authors conclude that even in cases where there could be a possible higher exposure to side-effects linked to the use of recombinant interferon alpha, still, the risk/benefit ratio suggests that recombinant interferon alpha 2b should be used for the treatment of hepatitis in elderly patients, in the light of the results obtained.


A paragon of self-tolerance: CD25+CD4+ regulatory T cells and the control of immune responses.
The interest in naturally arising regulatory T (TR) cells as a paradigm for maintaining immunological self-tolerance has undergone an explosive re-emergence in recent years. This renaissance was triggered by several key experimental observations and the identification of specific molecular markers that have enabled the isolation and experimental manipulation of these cells. Although their existence was once controversial, a large body of evidence now highlights the critical roles of TR cells in maintaining immunological self-tolerance. Furthermore, abnormality of natural TR cells can be a primary cause of autoimmune and other inflammatory diseases in humans.


The association between gestational weight gain and risk of stillbirth: a population-based cohort study.
To estimate the risk of stillbirth associated with excessive and inadequate weight gain during pregnancy. Retrospective cohort study using the Texas vital records database between 2006 and 2011, with 2,230,310 births (5502 stillbirths) was included for analysis. Pregnancies were categorized as adequate weight gain, excessive weight gain, inadequate weight gain, or weight loss based on the Institute of Medicine 2009 recommendations. Hazard ratios (HRs) for stillbirth were estimated for each gestational weight-gain stratum using adequate weight gain as the comparison group. The analysis was performed separately for each body mass index (BMI) class. Both inadequate weight gain and weight loss were associated with an increased risk of stillbirth for all BMI classes except the morbidly obese group. Highest risk was seen in weight-loss groups after 36 completed weeks (normal weight: HR = 18.85 [8.25-43.09]; overweight: HR = 5.87 [2.99-11.55]; obese: HR = 3.44 [2.34-5.05]). Weight loss was associated with reduced stillbirth risk in morbidly obese women between 24 and 28 weeks (HR = 0.56 [0.34-0.95]). Excess weight gain was associated with an increased risk of stillbirth among obese and morbidly obese women, with highest risk after 36 completed weeks (obese: HR = 2.00 [1.55-2.58]; morbidly obese: HR = 3.16 [2.17-4.62]). In contrast, excess weight gain was associated with reduced risk of stillbirth in normal-weight women between 24 and 28 weeks (HR = 0.57 [0.44-0.70]) and in overweight women between 29 and 33 weeks (HR = 0.62 [0.45-0.85]). Analysis for the underweight group was limited by sample size. Both excessive weight gain and inadequate weight gain were not associated with stillbirth in this group. Stillbirth risk increased with inadequate weight gain and weight loss in all BMI classes except the morbidly obese group, where weight demonstrated a protective effect. Conversely, excessive weight gain was associated with higher risk of stillbirth among obese and morbidly obese women but was protective against stillbirth in lower weight women.


Tumour marker acquisition in the polyp-to-cancer sequence in the colon.
Sequential studies of 6 tumour markers in an adenomatous polyp which eventually metastesized as adenocarcinoma are described. The findings suggest that with the development of malignancy, clones of cells with an increasing number of markers are favoured for continued growth and that this probably represents progressive gene derepression.


Phase shifts in circadian rhythmicity of total, free corticosterone and transcortine plasma levels in hypothyroid male Japanese quails.
Control, radiothyroidectomized, and methimasol-treated short day (6L:18D; beginning of light at 0700) male Japanese quails were studied with regard to their circadian rhythmicity of total, free corticosterone and transcortine plasma level. In the controls, the peak of total and free corticosterone coincided with the maximal corticosterone binding capacity of transcortine; these parameters can be characterized by similar daily rhythm. In hypothyroid birds a synchronous phase shift of these parameters has been observed. In methimasol-treated animals the phase shift of the circadian rhythmicity was 6-8 hr, and in the radiothyroidectomized group 12 hr, respectively. According to the degree of hypothyroidism the metabolic clearance rate (MCR) of corticosterone decreased. This effect leads to the phase shift of total corticosterone rhythm, and the shift includes not only free, but also transcortine concentration.


Investigation of the Gracilaria gracilis (Gracilariales, Rhodophyta) proteome response to nitrogen limitation.
Inorganic nitrogen has been identified as the major growth-limiting nutritional factor affecting Gracilaria gracilis populations in South Africa. Although the physiological mechanisms implemented by G. gracilis for adaption to low nitrogen environments have been investigated, little is known about the molecular mechanisms of these adaptions. This study provides the first investigation of G. gracilis proteome changes in response to nitrogen limitation and subsequent recovery. A differential proteomics approach employing two-dimensional gel electrophoresis and liquid chromatography-tandem mass spectrometry was used to investigate G. gracilis proteome changes in response to nitrogen limitation and recovery. The putative identity of 22 proteins that changed significantly (P < 0.05) in abundance in response to nitrogen limitation and recovery was determined. The identified proteins function in a range of biological processes including glycolysis, photosynthesis, ATP synthesis, galactose metabolism, protein-refolding and biosynthesis, nitrogen metabolism and cytoskeleton remodeling. The identity of fructose 1,6 biphosphate (FBP) aldolase was confirmed by western blot analysis and the decreased abundance of FBP aldolase observed with two-dimensional gel electrophoresis was validated by enzyme assays and western blots. The identification of key proteins and pathways involved in the G. gracilis nitrogen stress response provide a better understanding of G. gracilis proteome responses to varying degrees of nitrogen limitation and is the first step in the identification of biomarkers for monitoring the nitrogen status of cultivated G. gracilis populations.


Combining nitric oxide and calcium sensing for the detection of endothelial dysfunction.
Cardiovascular diseases are the leading cause of death worldwide and are not typically diagnosed until the disease has manifested. Endothelial dysfunction is an early, reversible precursor in the irreversible development of cardiovascular diseases and is characterized by a decrease in nitric oxide production. We believe that more reliable and reproducible methods are necessary for the detection of endothelial dysfunction. Both nitric oxide and calcium play important roles in the endothelial function. Here we review different types of molecular sensors used in biological settings. Next, we review the current nitric oxide and calcium sensors available. Finally, we review methods for using both sensors for the detection of endothelial dysfunction.


Iridescence in beef caused by multilayer interference from sarcomere discs.
Microscope photometry of raw and cooked iliocostalis was used to test the hypothesis that interference colours in beef may originate from reflections from sarcomere discs. Evidence in support of the hypothesis was, firstly, that interference colours were not altered by rotating a polarizer in the illumination pathway, or by rotating a polarizer in the measuring pathway. But when both pathways contained polarizers, iridescence was completely extinguished when the polarizers were crossed. Secondly, the reflectance spectra of interference colours all showed multiple interference peaks, with a major peak possibly originating from the top sarcomere and minor peaks originating from lower sarcomeres. Thirdly, major peaks were strongly dependent on the angle of measurement. Iridescence in beef is quite rare, but reflections from sarcomere discs may be a ubiquitous source of light scattering in meat.


Vibrio alginolyticus Associated Chronic Myringitis Acquired in Mediterranean Waters of Turkey.
Vibrio alginolyticus was originally classified as biotype 2 of Vibrio parahaemolyticus. Most clinical isolates are recovered from superficial wounds or the external ear infections. V. alginolyticus is acknowledged to be nearly nonpathogenic in humans. The reason for presence of V. alginolyticus's virulence is uncertain. We describe a chronic myringitis case in a 47-year-old female due to V. alginolyticus. According to her anamnesis, it was detected that she had sea bathing history in Mugla Coast in Turkey. Pure isolation of V. alginolyticus was obtained from external auditory canal's culture. Investigation and antimicrobial susceptibility of the isolate were performed by the automatized BD Phoenix system and Kirby-Bauer disk diffusion method, respectively. The bacteria were sensitive to all antibiotics. This case was presented to pay attention to Vibrio alginolyticus infections.


An efficient protocol to enhance recombinant protein expression using ethanol in Escherichia coli.
Bacterial cells can be engineered to express non-native genes, resulting in the production of, recombinant proteins, which have various biotechnological and pharmaceutical applications. In eukaryotes, such as yeast or mammalian cells, which have large genomes, a higher recombinant protein expression can be troublesome. Comparatively, in the Escherichia coli (E. coli) expression system, although the expression is induced with isopropyl β-d-1-thiogalactopyranoside (IPTG), studies have shown low expression levels of proteins. Irrespective of the purpose of protein production, the production process requires the accomplishment of three individual factors: expression, solubilization and purification. Although several efforts, including changing the host, vector, culture parameters of the recombinant host strain, co-expression of other genes and changing of the gene sequences, have been directed towards enhancing recombinant protein expression, the protein expression is still considered as a significant limiting step. Our protocol explains a simple method to enhance the recombinant protein expression that we have optimized using several unrelated proteins. It works with both T5 and T7 promoters. This protocol can be used to enhance the expressions of most of the proteins. The advantages of this technique are presented below:•It produces several fold increase in the expression of poorly expressed, less expressed or non-expressed recombinant proteins.•It does not employ any additional component such as chaperones, heat shock proteins or co-expression of other genes.•In addition to being inexpensive, easy to manage, universal, and quick to perform, the proposed method does not require any commercial kits and, can be used for various recombinant proteins expressed in the E. coli expression system.


Purification of a manganese-containing superoxide dismutase from Halobacterium halobium.
An oxygen-induced superoxide dismutase was purified from the halophilic bacterium, Halobacterium halobium, strain NRL. Due to the high salt requirement for enzyme stability, the purification had to be performed in the presence of 2 M NaCl. The pI of the protein was 4.95. The approximate Mr was 38,500. The subunit size as determined by sodium dodecyl sulfate-electrophoresis was approximately 19,000. Metal analysis showed 1.5 atoms of manganese per dimer, 0.5 atom zinc, and 1.54 atoms copper. The N-terminal sequence of amino acids was determined, and based upon the first 26 amino acids significant homology to other manganese- and iron-containing superoxide dismutases was revealed.


Facile development of Au-ring microelectrode for in vivo analysis using non-toxic polydopamine as multifunctional material.
In this study, we describe a facile and fast wet deposition technique to bottom-up fabricate Au-ring microelectrodes (Au-RMEs) using non-toxic polydopamine as multifunctional grafting material instead of commonly used (3-aminopropyl)-trimethoxysilane (APTMS). The Au-RMEs are fabricated by growing Au film uniformly inside of a pulled glass capillary. Au-RMEs with tip apex diameter ranging from 15 to 50 μm were fabricated involving four consequent steps, i.e. hydroxylating the inside wall of a pulled glass capillaries, grafting adhesive polydopamine (PDA) film to hydroxyl group surface, seeding gold nanoparticles (AuNPs) onto PDA surface and finally growing thickness-tunable gold layer on top of gold nanoparticles. After 3-mercaptopropionic acid (MPA) self-assembled monolayers (SAMs) modification, the Au-RMEs obtain improved specificity and sensitivity for monitoring of dopamine (DA) with respect to alleviating ascorbic acid (AA) interference. The current response is in wide linearity to DA concentration in the range of 0.2-100.0 μM with a correlation coefficient of 0.998 and the detection limit as low as 50.0 nM (S/N=3). In addition, the designed glass substrates of Au-RMEs were mechanically stronger and their tips can be further sharped by adjusting the pulling program. In order to demonstrate the utility of these fabricated microelectrodes in neurochemistry, Au-RMEs were used for electrochemical monitoring of DA release stimulated by K(+) in the striatum of rats. Thus, this study offers a novel and reliable strategy for preparing Au microelectrodes and maybe an attractive alternative to the traditional options for continuous and in vivo electrochemical monitoring of DA in various physiological processes.


Fluorescence recovery after photobleaching: application to nuclear proteins.
Fluorescence redistribution after photobleaching (FRAP) has received increasing attention ever since it was first introduced into cell biological research. The method was developed in the 1970s, when its biological application mainly focused on the mobility of fluorescently labelled constituents of the cell membrane. The development of confocal scanning microscopy in the 1980s facilitated accurate investigation of the behaviour of molecules in the inside of cells without specialised equipment. However, FRAP did not yet become as popular as it is today, probably because of the dedicated and time-consuming methodology required to purify and label proteins or other compounds and, moreover, to inject them into cells. The revolution created by the development of GFP-technology finally lead to a tremendous boost of FRAP applications in studying the behaviour of proteins in the living cells. Finally, the ongoing increase of speed and memory of personal computers allows computer modelling of FRAP experiments for analysis of complex 3-D FRAP data, and for the development of new FRAP assays. Here we discuss several variants of FRAP on the basis of its application to the investigation of the behaviour of proteins in the living cell nucleus.


Revisiting the 'One Material Fits All' Rule for Cancer Nanotherapy.
The promise of (nano)biomaterials for the treatment of cancer can only be realized following a comprehensive scrutiny of the tumor microenvironment. The generic use of 'inert' vehicles that deliver a specific cargo to treat a range of cancer types and disease states obeys the 'one material fits all' rule. However, this approach leads to suboptimal and unpredictable clinical outcomes. The key factors constructing the tumor milieu should guide the design of disease-responsive materials. Given the growing availability of nanomaterials for cancer therapy, a material that responds to each patient's needs and, hence, reacts in a graded manner based on disease cues, would pave the way to precision materials for cancer therapy.


A new micromethod for colorimetric determination of zinc in serum.
A simple micromethod with a colorimetric reagent of high sensitivity was developed for the determination of zinc in serum. For the color reagent 2-(2-pyridylazo)-5-dimethylaminophenol (PADAP) was used. Coefficients of variation of the within-day precision were 6.65 and 2.24% for zinc standard at concentrations of 0.1 and 0.5 microgram/ml, respectively. The mean recovery by this method was 101.2% (S.D.: 3.56%). Zinc concentrations measured by the above method showed good agreement with those by atomic absorption spectrophotometry, with a correlation coefficient of 0.934. Serum zinc values of 50 healthy adults (38 females, 12 males) ranged from 63 to 116 microgram/100 ml (mean: 89.68 microgram/100 ml, Sd.: 13.28 microgram/100 ml).


The influence of the quantity of food on fecundity in the desert grassland scorpion (Paruroctonus utahensis) (Scorpionida, Vaejovidae): An experimental test.
Females of the desert grassland scorpion Paruroctonus utahensis were maintained in field enclosures and fed differing amounts of food. The number of young scorpions per female varied from 0 to 32. The mean weight of second-instar young varied significantly among broods. The number of young, the size of the young, and total brood weight were not related to adult female size. There were no significant relationships between any of the brood characteristics and the amount of food eaten by the mother during the 11 month gestation. This suggests that foraging success is not an important proximate factor influencing fecundity in Paruroctonus utahensis.


Time on dialysis.
This article discusses the following three aspects of dialysis that are related primarily in that they deal with time (ie, the duration of dialysis treatments): (1) Which is better: long or short daily dialysis? (2) Does everyone need long dialysis? (3) How does time affect the measurement of the dialysis dose? As a working definition, short implies the least time necessary to provide equilibrated Kt/V or double-pool Kt/V (eKt/V) of 1.0 and remove intradialytic weight gain without symptoms. This article makes the following statements regarding time on dialysis: (1) The duration of the dialysis treatment for daily dialysis has different effects on the removal of small and large molecules. (2) Longer treatments are definitely indicated for some patients with poor compensation for rapid ultrafiltration. (3) Short treatments with high rates of clearance/volume are associated with more postdialysis urea rebond. It is therefore an advantage to express doses as equilibrated Kt/V.


Development of a clinical Multiple-Lunge Test to predict falls in older adults.
To develop a new Multiple-Lunge Test to distinguish between fallers and nonfallers in community-dwelling older adults. A cross-sectional design was used to establish the sensitivity and specificity of the test to predict faller status based on retrospective self-reported fall history. Local retirement villages. Community-dwelling older adults (N=130; mean age ± SD, 77±7y) with (n=40) and without (n=90) a history of falls. The Multiple-Lunge Test required individuals to lunge forward to a step length determined as 60% of their leg length, and return to start, for 5 consecutive repetitions. Interday and intraday test-retest reliability of the Multiple-Lunge Test was established across 2 testing occasions. Number of steps performed correctly, total time to complete 5 steps. The Multiple-Lunge Test was found to be reliable across trials (Intraday: intraclass correlation coefficient [ICC]=.79-.81 for steps, ICC=.86-.88 for time; Interday: ICC=.77 for steps; ICC=.84 for time). Sensitivity and specificity values were calculated as 73% and 63%, respectively, for predicting multiple fallers using the measure of all 5 steps done correctly. The test is easily administered and because of its challenging nature, it may be well suited to detect subtle differences in abilities of higher functioning, community-dwelling older adults. A practitioner can be confident in 7 of 10 cases that an older adult who cannot complete all 5 steps of the Multiple-Lunge Test is at high risk of falls. The results suggest that there is potential for the Multiple-Lunge Test to be used in clinical practice; however, additional research on how to further increase its validity appears warranted.


Glioblastoma multiforme of the conus medullaris with holocordal spread.
Glioblastoma multiforme of the conus medullaris is rare. It spreads both locally to contiguous structures and also by cerebrospinal seeding. The disease is aggressive and the ultimate prognosis is dismal. We report a case of conus medullaris glioblastoma multiforme with involvement of the holocord. In spite of excision of the conus medullaris tumor followed by radiation, the disease continued to progress rapidly. We discuss the rarity of the disease and the related literature with regard to treatment modalities.


Syndromes Associated with Sexually Transmitted Infections in Lilongwe, Malawi: Burden and Trends, 2006 to 2015.
Monitoring the burden of and trends in sexually transmitted infection syndromes is useful in informing syndromic management guidelines. Among sexually transmitted infection clinic patients in Lilongwe, Malawi, between 2006 and 2015, genital discharge, lower abdominal pain, and genital ulcer syndromes were common. Prevalence of most syndromes remained stable during the 10-year period.


Diagnosable and non-diagnosable causes of death by postmortem computed tomography: a review of 339 forensic cases.
Postmortem computed tomography (PMCT) is often used to diagnose causes of death, especially in nations with a low autopsy rate. To identify the causes of death that can and cannot be determined by PMCT, imaging findings were reviewed in 339 consecutive forensic autopsy cases. Causes of death could be determined based on PMCT findings alone in 7% of these cases, based on suggestive PMCT findings with additional information in 54%, and could not be determined by PMCT in 38%. PMCT screening may be useful for establishment of some causes of death, including traumatic intracranial hematoma, endogenous intracranial hemorrhage, and some cases of cardiac rupture. Suggestive findings from PMCT in other cases, such as those involving subarachnoid hemorrhage or pericardial hematoma, can lead to misdiagnosis and may be a pitfall of PMCT screening. Causes of death including some cases of cervical cord injuries, asphyxiation, burn, drug intoxication, acute myocardial infarction, and pulmonary thromboembolism cannot be diagnosed using PMCT.


Radiometric and spectroradiometric comparison of power outputs of five visible light-curing units.
The spectral distributions of the radiation emitted by five visible range curing lights were measured spectroradiometrically. The light intensities in specific wavelength bands were evaluated by graphical integration. The results were then compared with the instantaneous readings of power density of all of the units as measured with a commercial curing radiometer. The data obtained by both techniques correlated well at narrower specific wavelengths (450-500 nm), which are assumed to be more effective for photopolymerization. This finding indicates that curing radiometer is sensitive to the desired wavelengths and may be an effective tool to quickly characterize the curing efficiency of dental photocuring sources in a clinical setting.


Extraction of DNA from Human Skeletal Material.
In recent years the recovery and analysis of DNA from skeletal remains has been applied to several contexts ranging from disaster victim identification to the identification of the victims of conflict. Here are described procedures for processing the bone and tooth samples including mechanical and chemical cleaning, cutting and powdering in the presence of liquid nitrogen, complete demineralization of bone and tooth powder, DNA extraction, DNA purification using magnetic beads, and the precautions and strategies implemented to avoid and detect contamination. It has proven highly successful in the analysis of bones and teeth from Second World War victims' skeletal remains that have been excavated from mass graves in Slovenia and is also suitable for genetic identification of relatively fresh human remains.


Application of near infrared spectroscopy for rapid determination the geographical regions and polysaccharides contents of Lentinula edodes.
In this study, a calibration model based on Near-infrared spectroscopy (NIR) technique and chemometrics method was developed for rapid and non-destructive detecting the polysaccharide contents of lentinula edodes samples collected from different regions. The polysaccharide contents of these samples were firstly determined by standard phenol-sulphruic acid method. Then, NIR spectra of these samples were collected by using Fourier transform infrared spectrometry. Based on these experimental data, a random forest method was further used to distinguish the regions of these samples, with a classification accuracy of 96.6%. After that, a rapid, accurate, and quantitative model was established for predicting the polysaccharide contents of these samples. In the model establishing process, some signal pre-treatment methods were optimized, and the validation results with highest determination coefficient (R2) and low root mean square errors of prediction (RMSEP) were, 0.925 and 0.720, respectively. These results showed that combined NIR technique with chemometrics was an effective and green method for lentinula edodes quality control.


Autosomal-dominant pseudohypoparathyroidism type Ib is caused by different microdeletions within or upstream of the GNAS locus.
The term pseudohypoparathyroidism (PHP) refers to the different disorders that are caused by mutations within GNAS or upstream of this complex genetic locus. GNAS gives rise to several different transcripts, including Gsalpha (alpha-subunit of heterotrimeric stimulatory G protein), XLalphas (extra-large variant of Gsalpha), and several additional sense and antisense transcripts. The complexity of the GNAS locus is furthermore reflected by a parent-specific methylation pattern of most of its different promotors. PHP can be divided into two major groups, PHP type Ia (PHP-Ia) and PHP type Ib (PHP-Ib). PHP-Ia is caused by heterozygous mutations affecting one of the 13 GNAS exons encoding Gsalpha or by large intragenic deletions. In contrast, PHP-Ib is caused by heterozygous deletions within STX16, the gene-encoding syntaxin 16, which is located more than 220 kb upstream of GNAS, or by deletions within GNAS involving exon NESP55 and two of the antisense exons. In either form of PHP, hormonal resistance develops only after maternal inheritance of the mutation, while paternal inheritance of the same molecular defect is not associated with endocrine abnormalities. In most familial cases of PHP-Ib, there is a loss of exon A/B methylation combined with active A/B transcription from both parental alleles, which leads to suppression of Gsalpha transcription in the proximal renal tubules and, therefore, PTH resistance.


Churg-Strauss syndrome presenting with acute myocarditis and cardiogenic shock.
Churg-Strauss syndrome (CSS) is a multisystem disorder characterised by asthma, prominent peripheral blood eosinophilia, and vasculitis signs. We report the case of a 22 year-old man admitted to the intensive care unit for acute myocarditis complicated with cardiogenic shock. Eosinophilia, history of asthma, lung infiltrates, paranasal sinusitis, glomerulonephritis, and abdominal pain suggested the diagnosis of CSS. Cardiac MRI confirmed cardiac involvement with a diffuse subendocardial delayed enhancement of the left ventricular wall, and a left ventricular ejection fraction (LVEF) of 30%. Acute myocarditis was confirmed with myocardial biopsy. The patient was successfully treated with systemic corticosteroids, intravenous cyclophosphamide, vasopressor inotropes, intra-aortic balloon pump and mechanical ventilation, and was discharged 21 days later. One year after diagnosis, the patient was asymptomatic. The eosinophilic cell count was normal. Follow-up MRI at one year showed LVEF of 40% with persistent delayed enhancement. Cardiac involvement by CSS requires immediate therapy with corticosteroids and cyclophosphamide, which may allow recovery of the cardiac function.


Modulation of xylanase production from alkaliphilic Bacillus pumilus VLK-1 through process optimization and temperature shift operation.
This study was aimed at enhancing the production of xylanase from an alkaliphilic Bacillus pumilus VLK-1 in submerged fermentation using wheat bran, a cheap and abundantly available agro-residue, through process optimization and to monitor the effect of temperature shift operation on it. The potential of xylanase in saccharification of wheat straw was also investigated. The results showed that optimization of the fermentation process by one variable approach increased the enzyme yield from 402 to 4,986 IU/ml. Subsequently, optimization of nitrogen and carbon sources through response surface methodology led to high level xylanase production (7,295 IU/ml) which was 1.46-fold greater than one variable approach after 56 h of cultivation at 30 °C. Temperature shift operation during fermentation resulted in maximum xylanase production in lesser duration (48 h instead of 56 h). Enzymatic hydrolysis of the alkali pre-treated wheat straw with 500 IU xylanase alone released 173 ± 8 mg sugars/g whereas in combination with cellulase and β-glucosidase released 553 ± 12 mg sugars/g dry substrate in 6 h, indicating its potential in saccharification of the lignocellulosic substrate. Temperature shift operation is likely to be attractive for large scale industrial fermentation due to significant reduction in the operating cost. To our knowledge, this is the first report which showed the effect of temperature shift operation on xylanase production from bacteria. The xylanase production from Bacillus sp. in the present study is close to the highest titre reported in the literature. An enhanced xylanase production using wheat bran, a cheap and abundantly available agro-residue, will apparently reduce the enzyme cost, which would be beneficial for industry.


Resources and organisation in primary health care are associated with HbA1c level: A nationwide study of 230958 people with Type 2 diabetes mellitus.
To examine the association between personnel resources and organisational features of primary health care centres (PHCCs) and individual HbA1c level in people with Type 2 diabetes mellitus (T2DM). People with T2DM attending 846 PHCCs (n=230958) were included in this cross-sectional study based on PHCC-level data from a questionnaire sent to PHCCs in 2013 and individual-level clinical data from 2013 for people with T2DM reported in the Swedish National Diabetes Register, linked to individual-level data on socio-economic status and comorbidities. Data were analysed using a generalized estimating equations linear regression models. After adjusting for PHCC- and individual-level confounding factors, personnel resources associated with lower individual HbA1c level were mean credits of diabetes-specific education among registered nurses (RNs) (-0.02mmol/mol for each additional credit; P<0.001) and length of regular visits to RNs (-0.19mmol/mol for each additional 15min; P<0.001). Organisational features associated with HbA1c level were having a diabetes team (-0.18mmol/mol; P<0.01) and providing group education (-0.20mmol/mol; P<0.01). In this large sample, PHCC personnel resources and organisational features were associated with lower HbA1c level in people with T2DM.


Hyperglycemia increases infarct size in collaterally perfused but not end-arterial vascular territories.
Hyperglycemia exacerbates neuronal injury in the setting of reversible brain ischemia, but its effect on focal thrombotic infarction has been less extensively characterized. We investigated this problem in two rat models of focal vascular occlusion. In Model I, the right middle cerebral artery (MCA) was exposed via a subtemporal craniotomy in halothane- and nitrous oxide-anesthetized Wistar rats and was occluded photochemically by irradiation with an argon ion laser following the intravenous administration of the photosensitizing dye rose bengal. Permanent MCA occlusion was combined with temporary bilateral common carotid artery ligation. In Model II, similarly anesthetized Sprague-Dawley rats were subjected to permanent photochemical occlusion of the right MCA without common carotid occlusion. In both models, rats were food deprived for 24 h and were administered varying amounts of 50% dextrose (or saline) 15 min prior to vascular occlusion to produce a spectrum of plasma glucose values, ranging from 5 to 44 mumol/ml. Brains were examined histologically 7 days following vascular occlusion, and computer-assisted planimetry was used to compute infarct volumes. In Model I, the volume of neocortical infarction ranged from 30.3 to 108.4 mm3 and exhibited a strong linear correlation with increasing preischemic plasma glucose values (r = 0.70). In contrast, the size of the smaller striatal infarct in this model was not correlated with plasma glucose level. In Model II, there was a prominent striatal infarct, ranging in volume from 14.4 to 96.4 mm3, while neocortical infarction occurred inconstantly. As in Model I, striatal infarct volume in Model II showed no correlation with plasma glucose level.(ABSTRACT TRUNCATED AT 250 WORDS)


Excitability of the soleus H-reflex arc during walking and stepping in man.
In eight normal subjects, the excitability of the soleus (Sol) H-reflex was tested in parallel with Sol length changes, EMGs of leg and thigh muscles and ground contact phases, during three different pacing movements: bipedal treadmill walking, single limb treadmill walking, and single-limb stepping on one spot. A computerized procedure was used which compensated for changes in stimulus effectiveness that occurred during free motion. In the three paradigms examined, significant excitability modulations were observed with respect to a control level determined in standing weight-bearing position. During bipedal treadmill walking, excitability was decreased in the early stance, maximally enhanced in the second half of the stance, and again decreased during the end-stance and the whole swing phase, with a minimum value around the toe off period. The main modulation pattern was retained during single-limb treadmill walking. During single-limb stepping on one spot, the stance-phase increase in excitability and the swing phase depression were still present. However, in the second half of the swing phase, reflex responsiveness returned to reference level, which was maintained during the subsequent contact period. Moreover, a decrease in reflex excitability was detected around the mid-stance. The time course of the described modulations was only partly correlated with the EMG and length changes of the Sol muscle. Furthermore, in the three movements tested, during the early stance phase, the excitability of the H-reflex arc did not correspond to the one expected on the basis of the available H-reflex studies performed under static conditions. It is suggested that, at least in certain stride phases (e.g. around the early contact period), an active regulation affects the transmission in the Sol myotatic arc during the pacing movements investigated.


Coprisin-induced antifungal effects in Candida albicans correlate with apoptotic mechanisms.
Coprisin is a 43-mer defensin-like peptide from the dung beetle, Copris tripartitus. Here, we investigated the induction of apoptosis by coprisin in Candida albicans cells. Coprisin exerted antifungal and fungicidal activity without any hemolytic effect. Confocal microscopy indicated that coprisin accumulated in the nucleus of cells. The membrane studies, 1,6-diphenyl-1,3,5-hexatriene, calcein-leakage, and giant unilamellar vesicle assays, confirmed that coprisin did not disrupt the fungal plasma membrane at all. Moreover, the activity of coprisin was energy- and salt-dependent. Next, we investigated whether coprisin induced apoptosis in C. albicans. Annexin V-FITC staining and TUNEL assay showed that coprisin was involved with both the early and the late stages of apoptosis. Coprisin also increased the intracellular reactive oxygen species level, and hydroxyl radicals were included at high levels among the species. The effect of thiourea as a hydroxyl radical scavenger further confirmed the existence of the hydroxyl radicals. Furthermore, coprisin induced mitochondrial membrane potential dysfunction, cytochrome c release, and activation of metacaspases. In summary, this study suggests that coprisin could be a model molecule for a large family of novel antimicrobial peptides possessing apoptotic activity.


Profile analysis of emerging respiratory virus in children.
Acute respiratory infections (ARIs) are caused by a variety of microorganisms. Of all ARIs, 80% are caused by viruses such as human respiratory syncytial virus, metapneumovirus, influenza, parainfluenza, rhinovirus, and, more recently, Sars-CoV-2, which has been responsible for the COVID-19 pandemic. The objective of our study was to evaluate clinical data from a viral panel performed in children hospitalized with SARS or COVID-19 in the infirmary or ICU of 5 pediatric hospitals in the city of Goiânia, Goiás, Brazil. Demographic, clinical, and laboratory data were collected for analysis, and data on the outcomes underwent statistical treatment. A total of 128 patients were selected for the study, 54% of whom were male and 46% female. The viral panel included rhinovirus, COVID-19, metapneumovirus, adenovirus, and parainfluenza. Descriptive analyses of age profile showed differences in the involvement of particular viruses. The percentage of patients who required hospitalization in the ICU, infirmary, as well as individuals who were discharged after therapy or who died, were described. Our work shows that epidemiological surveillance measures are indispensable, especially if used in the continued analysis of viral panels in all pediatric patients with SARS.


The vasoactivity of the fetal lamb ductus arteriosus studied in utero.
The ductus arteriosus of the undisturbed fetal lamb was studied chronically by techniques that allowed direct serial measurements of the calibre of the fetal channel. When the direct actions were studied of vasoactive agents on the ductus arteriosus, prostaglandins did not dilate the vessel beyond its resting dimensions. The cyclooxygenase inhibitor, indomethacin, was a potent vasoconstrictor with a plateau of the dose-effect relationship occurring at 0.2 mg/kg. Fetuses of 95--98 days gestational age were equally sensitive to indomethacin when compared to animals near term. Although the prostaglandins, PGE1, PGE2 PGF2 alpha, PGH2, PGI2 and PGG2, had no direct effect on the ductus arteriosus, PGE1, PGE2, PGH2 and PGI2 reversed the vasoconstrictor action of indomethacin. Autonomic nervous system mediators and blockers, i.e., acetylcholine, atropine, norepinephrine, propranolol, phentolamine and methoxamine, had neither direct effects on the ductus arteriosus nor any influence of indomethacin-induced vasoconstriction. The same was true of angiotensin 1, angiotensin 2, blockade of conversion of angiotensin 1 to 2, serotonin, methysergide, aminophylline, adenosine, and dibutyryl cyclic AMP. Imidazole, a blocker of thromboxane synthase, had no direct effect on the ductus arteriosus, but reduced significantly the magnitude of the indomethacin constrictor action. The major finding of this investigation was the exquisite sensitivity of the ductus arteriosus to manipulations of the prostaglandin environment. The results suggest that both locally generated prostaglandins, as well as prostanoids in the circulation, may be involved in ductal patency and closure. A high degree of control is likely of the circulation of the ductus arteriosus and constriction of the fetal channel is probably the result of an active process.


Sacrifice in the face of foes: pathogen-induced programmed cell death in plants.
Inhibition of pathogen growth during the defense of plants is thought to involve a rapid process of cell death localized to the site of invasion. Recent studies suggest that the death of plant cells during this 'hypersensitive response' process is likely to result from the activation of a programmed cell death pathway.


Thalamocortical projections in the reeler mutant mouse.
The normal radial distribution of the different neocortical cell classes is inverted in the reeler mutant mouse. The organization of the thalamocortical projection in adult reelers has been investigated by using anterograde degeneration techniques. Thalamocortical axons follow anomalous trajectories to their target cytoarchitectonic fields in the mutant. After leaving the internal capsule, the axons ascend in sigmoid-shaped fascicles to enter a fiber stratum near the cortical surface. The axons course through this superficial stratum until they reach their target fields and then descend to terminate in deeper cortical planes. In the normal animal, by contrast, the axons course tangentially at the interface of the cortex with the subcortical white matter; upon reaching their target fields, they ascend to terminate more superficially in the cortex. Thus, in both genotypes the tangential portions of the axon trajectories pass through the polymorphic cell population. Both with respect to degree of divergence and the radial distribution of terminals within the different cytoarchitectonic fields, the thalamocortical projection in reeler, like that in the normal animal, appears to be composed of two distinct axon classes. The "class I" axons, the less-divergent system which terminates densely in two or three tiers within the cortex, are the subject of the present analysis. The "class I" projections form an orderly cortical representation of the thalamus: Despite distortions in the topography of the reeler thalamus and cortex, both the nucleus to field relationships and the detailed topologic organization of the projection appear to be normal. The terminals of class I projections are distributed in radially segregated tiers that resemble the tiered pattern of termination as in normal mice, and there are field-specific variations in the tiers that, like those of normal mice, are systematically related to variations of cortical cytoarchitecture. Thus, similar mechanisms, which may depend in part on the interaction of ingrowing axons with specific postsynaptic cell surfaces, must determine the restricted radial distribution of thalamocortical projections in both genotypes. However, there is an abnormal mix of somata and dendrites at all radial levels of the mutant cortex, suggesting that the spatial domain of termination of thalamocortical axons may be governed to some extent by factors other than the distribution of specific prospective postsynaptic cell surfaces. The reeler mutation alters the radial but not the tangential structure of the neocortex, suggesting that these two aspects of cortical organization develop under the control of independent mechanisms. The present results suggest that despite the anomalies of radial position, normal relationships between thalamocortical afferents and distinct classes of postsynaptic elements with characteristic radial distributions are largely conserved in reeler. Certain types of aberrant connections are highly probable, however.


Obtaining extracts rich in antioxidant polysaccharides from the edible mushroom Pleurotus ostreatus using binary system with hot water and supercritical CO2.
Pleurotus ostreatus is an edible mushroom with pharmacological potential, due to its metabolites, mainly polysaccharides. On here, the development of a new methodology for the recovery of extract rich in antioxidant polysaccharide was reported. The extracts were characterized, evaluated for antioxidant activity in vitro and in cell models and cytotoxicity. The best defined extraction condition was 25 MPa, 433.15 K, and 20% H2O, with 30.69% of the total yield and 0.921 mg of CHO3. The anomeric bonds, identified in the FTIR and NMR spectrum, indicate that the extracts are a mixture of heteropolysaccharides, β-glucans, α-glucans, and oligosaccharides. The best extraction condition has 80.83% of antioxidant activity, without cytotoxic effect in vitro. In addition to antioxidant activity in cell model, increasing protection against oxidative damage induced by H2O2. Finally, H2O + CO2-SFE technology can be used to obtain extracts rich in antioxidant polysaccharides with pharmacological and food potential.


Ovarian growth during larval development of queen and worker of Apis mellifera (Hymenoptera: Apidae): a morphometric and histological study.
The present work reports the differences between the ovarian grow in queen and worker larvae of A. mellifera, from the start of differential feeding. The observations made of the growth rates in larvae of both castes showed that the queen and worker larvae have the same rates of cephalic capsule growth from one instar to another but the weight gain is greater in queens. In the same way, the draw areas of ovaries of queens increase more and continuously, while from the 5th instar on the ovaries of workers decrease in size. The decrease is due to a loss of ovariole numbers that starts early in the worker larvae and increases in the 4th-5th instar. The ovarian shape in queens and workers became different in the last larval instars.


[Effect of armin on the ultrastructure of the neuromuscular synapse].
Alterations induced by the cholinesterase inhibitor armin (5.10(-7) g/ml) in the ultrastructure of motor nerve endings of the rat phrenic diaphragmal preparations at rest or electric stimulation of the nerve were studied. It was shown that armin at rest induced ultrastructural lesions in the endings similar to those in the control preparations during nerve stimulation. Electric stimulation did not produce additional changes in the ultrastructure of the neuromuscular junction under armin action. It is suggested that the disorder of the nerve ending function may be of importance in the mechanism of the blocking action of armin on the neuromuscular transmission.


[Changes in the large granular vesicles in sympathetic nerve endings under the influence of several pharmacologic agents].
Electron microscopic study of large dense-core vesicles of the adrenergic nerve endings in the middle cerebral arteries of some vertebrates showed substantial changes of the vesicles studied (in comparison with control) 60 to 70 minutes after rejections of ipraside (3 mg/kg) and dopamine (40 mg/kg). A statistically significant increase of their quantity was also revealed. Large dense-core vesicles are supposed to take part in the process of accumulation and transformation of noradrenaline and/or its precursors.


Large-scale brain network dynamics in very preterm children and relationship with socio-emotional outcomes: an exploratory study.
Children born very preterm (VPT; <32 weeks' gestation) are at high risk of neurodevelopmental and behavioural difficulties associated with atypical brain maturation, including socio-emotional difficulties. The analysis of large-scale brain network dynamics during rest allows us to investigate brain functional connectivity and its association with behavioural outcomes. Dynamic functional connectivity was extracted by using the innovation-driven co-activation patterns framework in VPT and full-term children aged 6-9 to explore changes in spatial organisation, laterality and temporal dynamics of spontaneous large-scale brain activity (VPT, n = 28; full-term, n = 12). Multivariate analysis was used to explore potential biomarkers for socio-emotional difficulties in VPT children. The spatial organisation of the 13 retrieved functional networks was comparable across groups. Dynamic features and lateralisation of network brain activity were also comparable for all brain networks. Multivariate analysis unveiled group differences in associations between dynamical functional connectivity parameters with socio-emotional abilities. In this exploratory study, the group differences observed might reflect reduced degrees of maturation of functional architecture in the VPT group in regard to socio-emotional abilities. Dynamic features of functional connectivity could represent relevant neuroimaging markers and inform on potential mechanisms through which preterm birth leads to neurodevelopmental and behavioural disorders. Spatial organisation of the retrieved resting-state networks was comparable between school-aged very preterm and full-term children. Dynamic features and lateralisation of network brain activity were also comparable across groups. Multivariate pattern analysis revealed different patterns of association between dynamical functional connectivity parameters and socio-emotional abilities in the very preterm and full-term groups. Findings suggest a reduced degree of maturation of the functional architecture in the very preterm group in association with socio-emotional abilities.


Necroptosis-mediated HMGB1 secretion of keratinocytes as a key step for inflammation development in contact hypersensitivity.
Keratinocyte necroptosis (with proinflammatory characteristic) is required for epidermal damage in contact hypersensitivity (CHS). In DNCB-induced CHS mice model, we observed the aggravated keratinocyte death and increased phosphorylation level of MLKL, RIPK3 and RIPK1. However, CHS skin lesion did not present in keratinocyte-specific Mlkl knockout mice. We validated that MLKL-mediated keratinocyte necroptosis is required for epidermal damage in response to immune microenvironment in CHS. Moreover, MLKL-mediated necroptosis deficiency or inhibition resulted in blocking recruitment and activation of inflammatory cells in CHS via reducing HMGB1 release in keratinocytes. This study suggests that MLKL-mediated keratinocyte necroptosis functions as a self-amplified actor in inflammatory responses and could be considered as an effective therapeutic target. It proposes an innovative prospective that inhibiting keratinocyte necroptosis can prevent the development of epidermal damage in CHS.


Diffusion-convection effects on drug distribution at the cell membrane level in a patch-clamp setup.
We present a model-based method for estimating the effective concentration of the active drug applied by a pressure pulse to an individual cell in a patch-clamp setup, which could be of practical use in the analysis of ligand-induced whole-cell currents recorded in patch-clamp experiments. Our modelling results outline several important factors which may be involved in the high variability of the electric response of the cells, and indicate that with a pressure pulse duration of 1s and diameter of the perfusion tip of 600 μm, elevated amounts of drug can accumulate locally between the pipette tip and the cell. Hence, the effective agonist concentration at the cell membrane level can be consistently higher than the initial concentration inside the perfusion tubes. We performed finite-difference and finite-element simulations to investigate the diffusion/convection effects on the agonist distribution on the cell membrane. Our model can explain the delay between the commencement of acetylcholine application and the onset of the whole-cell current that we recorded on human rhabdomyosarcoma TE671 cells, and reproduce quantitatively the decrease of signal latency with the concentration of agonist in the pipette. Results also show that not only the geometry of the bath chamber and pipette tip, but also the transport parameters of the diffusive and convective phenomena in the bath solution are determinant for the amplitude and kinetics of the recorded currents and have to be accounted for when analyzing patch-clamp data.


Low-flow aortic stenosis and preserved left ventricular ejection fraction.
Valvular aortic stenosis (AS) is the most frequent valvular disease in developed countries. Treatment decisions in AS are mainly based upon the symptomatic status of the patient and the severity of AS. Doppler echocardiography represents the standard tool for detecting and assessing the severity of the disease. Under the same denomination of severe AS [aortic valve area (AVA) < 1 cm(2)], several entities might be identified that differ in terms of trans-valvular flow rates and pressure gradients development. From a clinical standpoint, severe AS (AVA < 1 cm(2)) can be subdivided into 4 flow-gradient patterns: normal flow/low gradient (NF/LG), normal flow/high gradient (NF/HG), low flow/high gradient (LF/HG) and low flow/low gradient (LF/LG). The most commonly described entity is the paradoxical low-flow, low-gradient severe AS state, in which the stroke volume is unexpectedly reduced, despite preserved left ventricular (LV) ejection fraction. In daily practice, misdiagnosing this clinical condition might lead to an inappropriate timing of follow-up with an unnecessary delay of aortic valve replacement (AVR), which may, in turn, have a negative impact on patient outcome.


Low-fat diets for children: practicality and safety.
Despite our knowledge that atherogenesis begins in childhood and is attributable to dietary fat, pediatricians and dietitians generally frown on low-fat diets for children. It is the responsibility of clinicians to dispel the myths that make this conventional wisdom persist and encourage the adoption of a plant-based, low-fat diet. The consumption of adequate calories derived from plant-based foods will provide adequate minerals, protein, and calcium.


Metastatic hepatocellular carcinoma in the urinary bladder with radiation-induced hemorrhagic cystitis.
Metastatic hepatocellular carcinoma (HCC) to the urinary bladder is very rare. We present the case of a 58-year-old female patient who was diagnosed to have both HCC and cervical cancer. She developed hemorrhagic cystitis 2 years after radiation therapy for cervical cancer. During endoscopic electrocauterization for hemorrhagic cystitis, three small reddish tumors measuring less than 1 cm in diameter and with a raspberry-like appearance were found. Transurethral bladder tumor resection was performed. Pathology confirmed metastatic HCC to the bladder. Due to the similar appearance, these tumors are liable to be misinterpreted as engorged vessels secondary to irradiation if biopsies are not taken. Differential diagnosis by pathology is mandatory for such patients.


Effects of malnutrition on length of stay in patients hospitalized in an acute psychiatric ward.
Psychiatric patients are considered at risk for malnutrition due to pharmacological treatments, lifestyle habits and the mental illness by itself. Even though metabolic risk factors have been related to worse outcomes in certain conditions, the evidence regarding the nutritional status and its impact on the length of stay in psychiatric inpatients is scarce. This study aims to characterize the nutritional status in acute psychiatric patients, to correlate it with the length of stay, and to find specific potential indicators of malnutrition. Adult patients admitted to the Hospital Clínic of Barcelona acute psychiatric ward throughout a 1-year period were included in this cross-sectional study. Sociodemographic and clinical variables were registered, including length of stay and the nutritional status measured with the CONUT score. Malnutrition was observed in 42.5% of patients. Plasmatic transferrin saturation, protein and iron levels were inversely correlated with length of stay, having low iron levels an association with longer hospitalizations. The length of stay was not influenced by diagnosis or treatment. Negative correlations with the nutritional status were found in: BMI, cholesterol, triglycerides, albumin, total proteins, prealbumin, iron, lymphocytes and zinc levels, and transferrin saturation. The multivariate analysis showed a significant association for cholesterol and zinc levels, lymphocyte count, and BMI. Our results suggest that nutritional status might influence the course of psychiatric admissions. Cholesterol and zinc levels, lymphocyte count, and BMI might be factors strongly associated with malnutrition. This consideration might allow the identification of profiles in which lifestyle interventions could be implemented.


Effect of PDGF-BB combined with EDTA gel on adhesion and proliferation to the root surface.
Periodontal regeneration using EDTA or PDGF showed promising results, but the effect of combined application was still unclear. This study aimed to verify the effect of EDTA and/or PDGF application on root adhesion and proliferation of PDL fibroblast cells. Eighty specimens were prepared from forty periodontitis teeth and made five groups: (1) diseased (untreated), (2) SRP (scaling root planing), (3) EDTA (24%), (4) PDGF (25 ng/ml) and (5) Combined application of EDTA and PDGF. Periodontal ligament cells were cultured on the above conditioned dentin plate, and SEM examination was preformed and cells were counted within a representative standard area for both cell morphology and density. All groups including untreated showed significantly increase of adhered cells from baseline to 7 days. Among them, rate of increase was much higher in EDTA, PDGF, and combined groups. ANOVA test indicated that the number of cells in PDGF and combined groups was significantly higher than diseased group at 1 day. On day 7, PDGF and combined groups showed significantly higher number of adhesion cells than that found in the diseased, SRP and EDTA groups. Thus, root conditioning with EDTA enhanced cell adhesion more than SRP alone. There was no significant difference of cell number between PDGF and combined group. Combined application of EDTA and PDGF increased significantly PDL cell adhesion than EDTA alone. PDGF alone, however, also showed comparable effect to combined application at all periods. Thus, synergistic effect between PDGF and EDTA was not observed.


Complex endometrial hyperplasia and carcinoma in adolescents and young women 15 to 20 years of age. A report of 10 cases.
The clinical and histologic findings in 10 patients, 15-20 years of age, with complex hyperplasia or well-differentiated adenocarcinoma of the endometrium are presented. The morphologic distinction between the two lesions is discussed, and the frequency of misdiagnosis of this form of hyperplasia as carcinoma in this age group is emphasized. No difference was found in the behavior of the two lesions in this series of cases whether or not a hysterectomy was performed.


A proposed relationship between increases in the number of olfactory receptor neurons, convergence ratio and sensitivity in the developing rat.
In the rat neonate, as in other altricial young, olfaction, in contrast to vision and hearing, is functional at birth, being critically important in feeding, growth and other aspects of infant-mother interaction. Yet, olfactory sensitivity, i.e., the ability to detect odors at low levels, is poor in the newborn, improving dramatically in the first few postnatal weeks. To find a neural explanation for this phenomenon at the level of peripheral olfactory system, we present quantitative light microscopic data which reveal that during the suckling period of postnatal development the surface area of the olfactory receptor sheet and the total number of olfactory receptor neurons increase by about 8- and 12-fold respectively, being about 15 mm2 and 1.0 million on each nasal half of the newborn. Since the number of mitral cells, the principal relay neurons of the olfactory bulb, is already established at birth, at about 40,000 per olfactory bulb, it may be estimated that the convergence ratio of the olfactory neurons to mitral cells increases by more than 10-fold in the suckling period. We propose that the increased number of primary sensory afferent units and the higher convergence upon the central relay cells enhances the physiological capacities of the olfactory afferent pathway, increasing the opportunity for spatial summation and facilitation. The latter changes may lead to reduced olfactory thresholds and improved sensitivity with development. The relative contribution of these peripheral changes in enhancement of olfactory sensitivity during growth is discussed in the light of our knowledge on the developing olfactory system.


Elevated plasma levels of endothelin are associated with the severity of sepsis and presence of shock in contrast to the levels of atrial natriuretic peptide.
Immunoreactive endothelin (ETi) and atrial natriuretic peptide (ANPi) blood levels were measured by radioimmunoassay in patients with clinically defined sepsis. The interaction between these two peptides and their relation to circulatory shock and mortality were studied. All septic patients (n = 16) had significantly higher ETi (22.3 +/- 11.1 pg/ml) and ANPi (398.3 +/- 154.3 pg/ml) plasma concentrations compared to control subjects (ETi, 4.1 +/- 1.2; ANPi, 59.1 +/- 14.8 pg/ml; n = 13). ETi levels followed the severity of illness according to the APACHE II scoring system and were higher in patients who did not survive. ETi levels were significantly higher in the presence of shock and bacteraemia. Furthermore, ETi correlated well with plasma lactate (r = 0.83, p < 0.05), but not with renal function. ANPi levels did not show correlation with any of these determinants. Serial blood sampling, six consecutive days after admission, showed that ETi levels gradually decreased in normotensive patients in contrast to patients with septic shock. ANPi levels did not show systematic changes in time, and no relationship was observed between ETi and ANPi levels. These results suggest that plasma ETi levels are indicative for disease severity and might have prognostic significance. The role of ANPi during sepsis remains to be eludicated.


The burden and correlates of hypertension in rural Ghana: a cross-sectional study.
Cardiovascular diseases (CVDs), of which hypertension is a major risk factor, are predicted to account for four times as many deaths as from communicable diseases by the year 2020. Hypertension, once rare, is rapidly becoming a major public health burden in sub-Saharan Africa (SSA). However, data on its prevalence, awareness, treatment and control are paltry, especially for rural communities. This study was done to determine the burden and correlates of adult hypertension in the rural Barekese sub-district of Ghana. A cross-sectional survey was conducted on 425 adults aged ≥ 35 in the Barekese sub district (estimated population 18,510). Socio-demographic characteristics, modifiable and non-modifiable risk factors, blood pressure (BP) and anthropometric measurements were collected using standardized protocols. Overall, the proportion of hypertension and isolated systolic hypertension is 44.7% and 32.7% respectively in the study population. However, 64.9% of these were on treatment, with only 8.9% having controlled blood pressure (<140/90 mmHg). The mean systolic and diastolic BP were 134.38 mmHg (standard deviation, SD: 21.46) and 84.32 mmHg (SD: 12.44). Obesity (Body Mass Index, BMI>30 kg/m²) was found in 37 (10.4% of the population), out of whom 7 (15.9%) were extremely obese (BMI> 40 kg/m²). Increasing age and level of education were positively correlated with increasing blood pressure. The high burden of hypertension in this population along with the considerable less detection, treatment and control is of great concern. There is the need to promote health education measures that will foster prevention and early detection of hypertension.


Physiological range of peak cardiac power output in healthy adults.
The purpose of this study was to indicate the normal range for peak cardiac power output (CPO(peak)) in healthy adults and to explore age- and sex-related variations of this parameter. Using the non-invasive exponential CO(2) rebreathing technique [J.G. Defares, J Appl Physiol13 (1958) 159], cardiac output was measured at an exercise intensity determined to coincide with > or =95% of peak oxygen consumption in 102 healthy adults (mean +/- SD, age 43 +/- 13 years, body mass 74 +/- 13 kg). Peak cardiac power was then computed from measurements of peak cardiac output (Q(Tpeak)) and peak mean arterial pressure (MAP(peak)) using the equation described by Cooke et al. [Heart79 (1998) 289]. Peak oxygen consumption in the study population was 2.42 (+/-0.74) l min(-1) and subjects achieved 101 +/- 7% of this value during the measurement of . was 17.3 (+/-4) l min(-1), and CPO(peak) was computed as 4.5 (+/-1.2) W. CPO(peak) ranged from 3.11 to 7.94 W in men and 2.53 to 5.57 W in women. Additionally, ageing appears to be associated with a significant loss of peak cardiac power in men that is not apparent in women. Although the sample size remains moderate, the CPO values attained were normally distributed and these values provide a useful indication of the normal range for CPO(peak) in healthy adults.


Linkage of TP53 codon 72 pro/pro genotype as predictive factor for nasopharyngeal carcinoma development.
Genetic predisposition has been suggested as a cofactor for cancer aetiology and a polymorphism in TP53 codon 72 has been associated as a susceptibility factor for several cancers. Nasopharyngeal carcinoma is a rare neoplasia in western civilizations and genetic predisposition might play an important role in its development. We evaluated the linkage of the polymorphic variants (Arg/Pro) on TP53 codon 72 with nasopharyngeal cancer development in a case-control study with 392 individuals from a northern Portuguese population, including 107 patients with nasopharyngeal carcinoma and 285 healthy controls. This study revealed a three-fold risk for carriers of Pro/Pro genotype either against carriers of Arg/Arg (OR=2.62; 95% CI=1.10-6.30; P=0.016) or total Arg carriers (OR=2.67; 95% CI=1.21-5.90; P=0.012). Moreover, step-wise logistic regression analysis identified Pro/Pro genotype (OR=3.1; 95% CI=1.3-7.3; P=0.009), age >49 at diagnosis (OR=2.5; 95% CI=1.6-4.0; P<0.001) and male gender (OR=2.7; 95% CI=1.6-4.4; P<0.001) as predictive factors for the development of nasopharyngeal carcinoma. These results confirm the data from Asiatic populations suggesting that Pro/Pro genotype represents a stable risk factor for nasopharyngeal carcinoma development in Portugal and that TP53 codon 72 polymorphism can contribute as a genetic susceptibility marker, providing additional information to improve the knowledge about nasopharyngeal carcinoma aetiology.


Theta Phase Synchronization Is the Glue that Binds Human Associative Memory.
Episodic memories are information-rich, often multisensory events that rely on binding different elements [1]. The elements that will constitute a memory episode are processed in specialized but distinct brain modules. The binding of these elements is most likely mediated by fast-acting long-term potentiation (LTP), which relies on the precise timing of neural activity [2]. Theta oscillations in the hippocampus orchestrate such timing as demonstrated by animal studies in vitro [3, 4] and in vivo [5, 6], suggesting a causal role of theta activity for the formation of complex memory episodes, but direct evidence from humans is missing. Here, we show that human episodic memory formation depends on phase synchrony between different sensory cortices at the theta frequency. By modulating the luminance of visual stimuli and the amplitude of auditory stimuli, we directly manipulated the degree of phase synchrony between visual and auditory cortices. Memory for sound-movie associations was significantly better when the stimuli were presented in phase compared to out of phase. This effect was specific to theta (4 Hz) and did not occur in slower (1.7 Hz) or faster (10.5 Hz) frequencies. These findings provide the first direct evidence that episodic memory formation in humans relies on a theta-specific synchronization mechanism.


Platinum salts in the treatment of BRCA-associated breast cancer: A true targeted chemotherapy?
Germline pathogenic mutations in breast cancer (BC) susceptibility genes (gBRCA1/2) are the most frequent inherited alterations in BC and are involved in the homologous recombination pathway, the principal mechanism of DNA double strand break repair. Platinum salts which act as DNA cross-linking agents are therefore more likely to be active in BRCA-deficient tumors. Women with gBRCA-associated tumors, particularly with triple negative BC, receiving neoadjuvant platinum containing regimens achieved higher pCR rates as compared to wild-type BC. However in two large randomized trials the addition of carboplatin significantly increased pCR rate only in wild-type tumors. On the contrary, the randomized TNT trial showed a significant benefit for carboplatin vs docetaxel in terms of response rate and PFS specifically in patients with advanced gBRCA -associated tumors. Biomarkers of sensitivity to DNA damaging agents beyond gBRCA mutations predicting activity of platinum salts have been proposed and should be validated prospectively.


Phonon vibrational frequencies of all single-wall carbon nanotubes at the lambda point: reduced matrix calculations.
With a simple method-the reduced matrix method, we simplified the calculation of the phonon vibrational frequencies according to SWNTs structure and their phonon symmetric property and got the dispersion properties of all SWNTs at Gamma point in Brillouin zone, whose diameters lie between 0.6 and 2.5 nm. The calculating time is shrunk about 2-4 orders. A series of the dependent relationships between the diameters of SWNTs and the frequencies of Raman and IR active modes are given. Several fine structures including "glazed tile" structures in omega approximately d figures are found, which might predict a certain macro-quantum phenomenon of the phonons in SWNTs.