The modified 2VO ischemia protocol causes cognitive impairment similar to that induced by the standard method, but with a better survival rate

Permanent bilateral occlusion of the common carotid arteries (2VO) in the rat has been established as a valid experimental model to investigate the effects of chronic cerebral hypoperfusion on cognitive function and neurodegenerative processes. Our aim was to compare the cognitive and morphological outcomes following the standard 2VO procedure, in which there is concomitant artery ligation, with those of a modified protocol, with a 1-week interval between artery occlusions to avoid an abrupt reduction of cerebral blood flow, as assessed by animal performance in the water maze and damage extension to the hippocampus and striatum. Male Wistar rats (N = 47) aged 3 months were subjected to chronic hypoperfusion by permanent bilateral ligation of the common carotid arteries using either the standard or the modified protocol, with the right carotid being the first to be occluded. Three months after the surgical procedure, rat performance in the water maze was assessed to investigate long-term effects on spatial learning and memory and their brains were processed in order to estimate hippocampal volume and striatal area. Both groups of hypoperfused rats showed deficits in reference (F(8,172) = 7.0951, P < 0.00001) and working spatial memory [2nd (F(2,44) = 7.6884, P < 0.001), 3rd (F(2,44) = 21.481, P < 0.00001) and 4th trials (F(2,44) = 28.620, P < 0.0001)]; however, no evidence of tissue atrophy was found in the brain structures studied. Despite similar behavioral and morphological outcomes, the rats submitted to the modified protocol showed a significant increase in survival rate, during the 3 months of the experiment (P < 0.02).

Follow-up of patients treated with retinoic acid for the control of radioiodine non-responsive advanced thyroid carcinoma

During thyroid tumor progression, cellular de-differentiation may occur and it is commonly accompanied by metastatic spread and loss of iodine uptake. Retinoic acid (RA) administration might increase iodine uptake in about 40% of patients, suggesting that RA could be a promising therapeutic option for radioiodine non-responsive thyroid carcinoma, although a prospective study with a long-term follow-up has not been reported. This was a clinical prospective study assessing the value of 13-cis-RA in patients with advanced thyroid carcinoma and its impact on major outcomes such as tumor regression and cancer-related death with a long-term follow-up of patients submitted to radioiodine (131I) therapy after RA administration. Sixteen patients with inoperable disease and no significant radioiodine uptake on post-therapy scan were selected. Patients were treated orally with 13-cis-RA at a dose of 1.0 to 1.5 mg·kg-1·day-1 for 5 weeks and then submitted to radioiodine therapy (150 mCi) after thyroxine withdrawal. A whole body scan was obtained 5 to 7 days after the radioactive iodine therapy. RECIST criteria were used to evaluate the response. An objective partial response rate was observed in 18.8%, a stable disease rate in 25% and a progression disease rate in 56.2%. Five patients died (62.5%) in the group classified as progression of disease. Progression-free survival rate (PFS) ranged from 72 to 12 months, with a median PFS of 26.5 months. RA may be an option for advanced de-differentiated thyroid cancer, due to the low rate of side effects.

Advanced glycation end products (AGEs) and their receptor (RAGE) induce apoptosis of periodontal ligament fibroblasts

Diabetics have an increased prevalence of periodontitis, and diabetes is one of the causative factors of severe periodontitis. Apoptosis is thought to be involved in this pathogenic relationship. The aim of this study was to investigate apoptosis in human periodontal ligament (PDL) fibroblasts induced by advanced glycation end products (AGEs) and their receptor (RAGE). We examined the roles of apoptosis, AGEs, and RAGE during periodontitis in diabetes mellitus using cultured PDL fibroblasts that were treated by AGE-modified bovine serum albumin (AGE-BSA), bovine serum albumin (BSA) alone, or given no treatment (control). Microscopy and real-time quantitative PCR indicated that PDL fibroblasts treated with AGE-BSA were deformed and expressed higher levels of RAGE and caspase 3. Cell viability assays and flow cytometry indicated that AGE-BSA reduced cell viability (69.80±5.50%, P<0.01) and increased apoptosis (11.31±1.73%, P<0.05). Hoechst 33258 staining and terminal-deoxynucleotidyl transferase-mediated nick-end labeling revealed that AGE-BSA significantly increased apoptosis of PDL fibroblasts. The results showed that the changes in PDL fibroblasts induced by AGE-BSA may explain how AGE-RAGE participates in and exacerbates periodontium destruction.

Metronomic chemotherapy in the neoadjuvant setting: results of two parallel feasibility trials (TraQme and TAME) in patients with HER2+ and HER2− locally advanced breast cancer

Neoadjuvant chemotherapy has practical and theoretical advantages over adjuvant chemotherapy strategy in breast cancer (BC) management. Moreover, metronomic delivery has a more favorable toxicity profile. The present study examined the feasibility of neoadjuvant metronomic chemotherapy in two cohorts [HER2+ (TraQme) and HER2− (TAME)] of locally advanced BC. Twenty patients were prospectively enrolled (TraQme, n=9; TAME, n=11). Both cohorts received weekly paclitaxel at 100 mg/m2 during 8 weeks followed by weekly doxorubicin at 24 mg/m2 for 9 weeks in combination with oral cyclophosphamide at 100 mg/day (fixed dose). The HER2+ cohort received weekly trastuzumab. The study was interrupted because of safety issues. Thirty-six percent of patients in the TAME cohort and all patients from the TraQme cohort had stage III BC. Of note, 33% from the TraQme cohort and 66% from the TAME cohort displayed hormone receptor positivity in tumor tissue. The pathological complete response rates were 55% and 18% among patients enrolled in the TraQme and TAME cohorts, respectively. Patients in the TraQme cohort had more advanced BC stages at diagnosis, higher-grade pathological classification, and more tumors lacking hormone receptor expression, compared to the TAME cohort. The toxicity profile was also different. Two patients in the TraQme cohort developed pneumonitis, and in the TAME cohort we observed more hematological toxicity and hand-foot syndrome. The neoadjuvant metronomic chemotherapy regimen evaluated in this trial was highly effective in achieving a tumor response, especially in the HER2+ cohort. Pneumonitis was a serious, unexpected adverse event observed in this group. Further larger and randomized trials are warranted to evaluate the association between metronomic chemotherapy and trastuzumab treatment.

Comparison of totally tubeless percutaneous nephrolithotomy and standard percutaneous nephrolithotomy for kidney stones: a randomized, clinical trial

This study aimed to compare the totally tubeless percutaneous nephrolithotomy and standard percutaneous nephrolithotomy techniques regarding their rates of success and complications in patients with kidney stones. Patients were randomly assigned to two groups. Forty-four patients (24 men; mean age: 50.40±2.02 years) received totally tubeless percutaneous nephrolithotomy (PCNL; no nephrostomy catheter or ureteral catheter after PCNL) and 40 patients (18 men; mean age: 49.95±13.38 years) underwent standard PCNL (a nephrostomy catheter and ureteral catheter were used after PCNL). All surgeries were performed by one surgeon. Postoperative changes in hemoglobin, the blood transfusion rate, changes in creatinine levels, operation time, analgesic need, hospitalization time, and complication rate were compared between the groups. No significant differences were observed in age, gender, stone size, and surgery side between the groups (P<0.05). The operation time was significantly lower in the totally tubeless PCNL group than in the standard PCNL group (P=0.005). Pethidine requirements were significantly higher in the standard PCNL group than the totally tubeless PCNL group (P=0.007). Hospitalization time was significantly higher in the standard PCNL group than in the totally tubeless PCNL group (P<0.0001). The complication rate was 15% in the standard PCNL group and 9.1% in the totally tubeless PCNL group (P=0.73). The totally tubeless PCNL technique is safe and effective, even for patients with staghorn stones. This technique is associated with decreased pain, analgesic needs, and operative and hospitalization time. We believe that a normal peristaltic ureter is the best drainage tube.

Characterization of maturity and quality of Brazilian apirenic grapes in the São Francisco river Valley

The objective of this study was to characterize and correlate maturity and quality of the first varieties of Brazilian seedless grapes 'BRS Clara', 'BRS Linda', 'BRS Morena', and 'Advanced Selection 8' compared with the American variety 'Crimson Seedless' in compliance with the Brazilian Normative/2002 and export standards Advanced Selection 8' is dark reddish, has large clusters, and is a very large ellipsoid berry; 'BRS Morena' is black with medium sized clusters and large berry shaped as ellipsoid to globoid; 'BRS Linda' is light green and has large sized clusters; 'Crimson' is pink and has small clusters with berries varying from medium to large sizes and ellipsoid shaped; and 'BRS Clara' is green yellowish has medium sized clusters and small berry of elongated ellipsoid shape. All varieties evaluated meet the standard for domestic market established as berry size minimum diameter 12 mm. 'BRS Clara' does not meet the export requirements of diameter. Berries of the red grapes 'BRS Morena' and 'Crimson Seedless' are firmer. The pH, titratable acidity, and soluble solids meet the official standards. Larger clusters are less acidic and present higher soluble solids/titratable acidity ratios implying that they are the sweetest type when ripe.

Effect of standard and neutral-pH peritoneal dialysis solutions upon fibroblasts proliferation

Introduction: Continuous exposition of the peritoneal membrane to conventional dialysis solutions is an important risk factor for inducing structural and functional alterations. Objective: To compare in vitro mouse fibroblast NIH-3T3 cell viability after exposition to a neutral pH dialysis solution in comparison to cells exposed to a standard solution. Methods: Experimental study to compare the effects of a conventional standard or a neutral-pH, low-glucose degradation products peritoneal dialysis solution on the viability of exposed fibroblasts in cell culture. Both solutions were tested in all the commercially available glucose concentrations. Cell viability was evaluated with tetrazolium salt colorimetric assay. Results: Fibroblast viability was significantly superior in the neutral pH solution in comparison to control, in all three glucose concentrations (Optical density in nm-means ± SD: 1.5% 0.295 ± 0.047 vs. 0.372 ± 0.042, p < 0.001; 2.3% 0.270 ± 0.036 vs. 0.337 ± 0.051, p < 0.001; 4.25% 0.284 ± 0.037 vs. 0.332 ± 0.032, p < 0.001; control vs. neutral pH respectively, Student t Test). There was no significant difference in cell viability between the three concentrations of glucose when standard solution was used (ANOVA p = 0.218), although cell viability was higher after exposition to neutral pH peritoneal dialysis fluid at 1.5% in comparison to 2.3 and 4.25% glucose concentrations (ANOVA p = 0.008: Bonferroni 1.5% vs. 2.3% p = 0.033, 1.5% vs. 4.25% p = 0.014, 2.3% vs. 4.25% p = 1.00). Conclusion: Cell viability was better in neutral pH dialysis solution, especially in the lower glucose concentration. A more physiological pH and lower glucose degradation products may be responsible for such results.

Analysis and guidelines for implementation of EN 1090-2 Standard to assist execution class assignment of steel structures

Finnish design and consulting companies are delivering robust and cost-efficient steel structures solutions to a large number of manufacturing companies worldwide. Recently introduced EN 1090-2 standard obliges these companies to specify the execution class of steel structures for their customers. This however, requires clarifying, understanding and interpreting the sophisticated procedure of execution class assignment. The objective of this research is to provide a clear explanation and guidance through the process of execution class assignment for a given steel structure and to support the implementation of EN 1090-2 standard in Rejlers Oy, one of Finnish design and consulting companies. This objective is accomplished by creating a guideline for designers that elaborates on the four-step process of the execution class assignment for a steel structure or its part. Steps one to three define the consequence class (projected consequences of structure failure), the service category (hazards associated with the service use exploitation of steel structure) and the production category (manufacturing process peculiarities), based on the ductility class (capacity of structure to withstand deformations) and the behaviour factor (corresponds to structure seismic behaviour). The final step is the execution class assignment taking into account results of previous steps. Main research method is indepth literature review of European standards family for steel structures. Other research approach is a series of interviews of Rejlers Oy representatives and its clients, results of which have been used to evaluate the level of EN 1090-2 awareness. Rejlers Oy will use the developed novel coherent standard implementation guideline to improve its services and to obtain greater customer satisfaction.

The impact on advanced economies of north-south trade in manufacturing and services

Many types of production are being transferred from the rich economies of the North to the poorer economies of the South. Such changes began in manufacturing but are now spreading to services. This paper provides estimates of their past and future impact on employment in the North. About 5 million manufacturing jobs have been lost over the past decade because of trade with low-wage economies. A similar number of service jobs may be lost to low-wage economies over the next decade. Although small compared to total employment, such losses may seriously harm certain localities or types of worker.

Pienten yhtiöiden tilintarkastusstandardin arvioitu vaikutus tilintarkastuksen hyötyihin – Standard for Audits of Small Entities, SASE

Suomessa ja muissa Pohjoismaissa on tunnistettu haasteita kansainvälisten tilintarkastusstandardien eli ISA-standardien soveltamisessa pienten yhtiöiden tilintarkastuksiin. ISA-standardien on kritisoitu sisältävän liian yksityiskohtaisia ja jopa epärealistisia vaatimuksia ajatellen pienien yhtiöiden tilintarkastuksia. Pohjoismaisella yhteistyöllä onkin alettu kehittää omaa standardia pienten yhtiöiden tilintarkastuksiin. Niin sanotun SASE-standardin on raportoitu muun muassa korostavan tilintarkastajan ammatillista harkintaa ja keventävän pienten yhtiöiden tilintarkastuksen vaatimuksia. Koska kuitenkin aikaisemmin sääntelyn lisäämisellä on pyritty muun muassa lisääntyneeseen tilintarkastuksen luotettavuuteen, josta myös pienten yhtiöiden on itse tutkittu hyötyvän, on tutkimuksessa haluttu selvittää, miten kehitteillä olevan SASE-standardin arvioidaan vaikuttavan yleisesti pienten yhtiöiden tilintarkastuksella saavutettaviin hyötyihin. Tutkimus on toteutettu toiminta-analyyttisena laadullisena tutkimuksena, ja tutkimusmetodina on käytetty tilintarkastajien ja yliopiston tutkijatohtorin haastatteluja. Tutkimuksen tulosten mukaan kehitteillä olevan SASE-standardin arvioidaan vaikuttavan pienten yhtiöiden tilintarkastuksen hyötyihin kaksisuuntaisesti. Toisaalta SASE-standardi voi lisätä tilintarkastuksen hyötyjä, koska tilintarkastaja voisi keskittyä tarkastuskohteen kannalta olennaisempiin asioihin, hyödyntää hiljaista tietoaan sekä lisätä vuorovaikutusta yhtiön omistajajohdon kanssa. SASE-standardin ei arvioida muuttavan juurikaan käytännön tilintarkastustyötä ja periaatteessa olennaisuuksiin keskittymisen ja riskien tehokkaamman tunnistamisen tulisi hyödyttää myös tilintarkastuskohteen ulkoisia sidosryhmiä, kuten rahoittajia. Kuitenkin tutkimuksessa nousi esiin SASE-standardin mahdollinen heikko maine. Mikäli SASE-standardia pidettäisiin vähäpätöisempänä tai epäluotettavampana kuin aikaisempaa käytäntöä, luottamus tilintarkastusta ja tarkastuskohdetta kohtaan heikkenisi ja sitä kautta myös tilintarkastuksen hyödyt pienenisivät. Tutkimuksen johtopäätöksenä voidaan esittää, että tilintarkastuksen sääntelyn keventämisen vaikutus tilintarkastuksen hyötyihin ei niinkään synny käytännön työn kautta. Tilintarkastuksen hyötyihin pikemminkin vaikuttavat maineeseen, viestintään ja vuorovaikutukseen liittyvät seikat. Toimivalla vuorovaikutuksella yhtiön omistajajohdon ja tilintarkastajan välillä voidaan tilintarkastuksen hyötyjä korostaa, ja toisaalta taas riittävällä ulkoisiin sidosryhmiin kohdistuvalla tiedottamisella voidaan hyötyjen heikkenemistä ehkäistä. Keskeiseksi seikaksi tutkimuksessa nousee se, että tilintarkastuksen luotettavuuden ja tason säilyminen on pystyttävä todistamaan.

Interoperability for IoT Health Systems Using HL7 Standard

Internet of Things or IoT is revolutionizing the world we are living in, similarly the way Internet and the web did few decades ago. It is changing how we interact with the things surrounding us. Electronic health and remote patient monitoring are the ways of utilizing these technological improvements towards the healthcare. There are many applications of IoT in eHealth such as, it will open the gate to provide healthcare to the remote areas of the world, where healthcare through traditional hospital systems cannot be provided. To connect these new eHealth IoT systems with the existing healthcare information systems, we can use the existing interoperability standards commonly used in healthcare information systems. In this thesis we implemented an eHealth IoT system based on Health Level 7 interoperability standard for continuous data transmission. There is not much previous work done in implementing the HL7 for continuous sensor data transmission. Some of the previous work was limited to sensors which are not continuous in nature and some of it is only theatrical architecture. This thesis aims to prove that it is possible to implement an eHealth IoT system by using sensors which require continues data transmission, such as respiratory sensors, and to connect it with the existing eHealth information system semantically by using HL7 interoperability standard. This system will be beneficial in implementing eHealth IoT systems for those patients, who requires continuous healthcare personal monitoring. This includes elderly people and patients, whose health need to be monitored constantly. To implement the architecture, HL7 v2.5 is selected due to its ease of implementation and low size. We selected some open source technologies because of their open licenses and large developer community. We will also review the most efficient technology available in every layer of eHealth IoT system and will propose an efficient system.