Elektroencefalografske, elektrokardigrafske i spirometrijske promjene u koza uzrokovane propofolom

The effects of Propofol-induced electroencephalographic, electrocardiographic and spirometric changes were studied at a lower dose rate (0.4 mg/kg body mass, intravenously) and at higher dose rate (0.5 mg/kg body mass, intravenously) in four apparently healthy goats 10 to 14 months old, weighing 9 to 12 kg. Electroencephalographic results showed that anesthesia was induced with a change of distorted β wave patterns to α waves within one minute. The α wave patterns continued for 5 to 6 minutes at the lower dose (0.4 mg/kg body mass) while they persisted for 12 to 13 minutes at the higher dose (0.5 mg/kg body mass). At the lower dose, recovery was predictable after 5 minutes on reversal of the EEG pattern from α to β waves, whereas at the higher dose α wave patterns continued for 15 minutes. The occurrence of the righting reflfl ex was noticed after the disappearance of α waves. The heart rate increased with both the dose rates within the fifi rst 5 minutes and decreased after 10 and 15 minutes of induction. Inverted T waves were found in two goats at the lower dose while at the higher dose it was found to be inverted in three of the four goats. One of the goats inducted with the higher dose showed tachycardia, with ectopic beats from the 5th to 7th minute post induction. On average, apnea was noticed for the fifi rst 30 seconds at the lower dose and for 42 seconds at the higher dose. One of the animals receiving the higher dose showed apnea for 314 seconds. This goat was given artififi cial respiration after 106 seconds and then again after 296 seconds to resuscitate it. The animal showed severe respiratory distress with abdominal respiration during the fifi rst few seconds. The tidal volume did not return to normal until 15 minutes after induction. This indicates that Propofol has a respiratory depressant activity in goats and positive pressure ventilation must be provided. It does not induce analgesia and should be accompanied by analgesics .Istraživane su elektroencefalografske, elektrokardiografske i spirometrijske promjene uzrokovane propofolom u četiri zdrave koze u dobi od 10 do 14 mjeseci, mase od 9 do 12 kg. Propofol im je bio primijenjen intravenski u malim (0,4 mg/kg tjelesne mase) i većim (0,5 mg/kg tjelesne mase) dozama. Rezultati elektroencefalografi je pokazali su da se pri izazvanoj anesteziji obrazac β vala promijenio u α valove u tijeku jedne minute. Obrasci α vala nastavili su se tijekom 5 do 6 minuta kod primjene male doze (0,4 mg/kg tjelesne mase) dok su kod primjene veće doze (0,5 mg/kg tjelesne mase) trajali 12 do 13 minuta. Kod primjene manje doze oporavak se mogao očekivati nakon pet minuta s povratkom EEG obrasca s α na β val, dok je kod većih doza α val trajao do 15 minuta. Pojava refleksa dizanja bila je zapažena nakon nestanka α valova. Učestalost srčanih otkucaja povećala se kod primjene obiju doza tijekom prvih pet minuta, a smanjila se nakon 10 i 15 minuta. Negativan T val bio je ustanovljen u dvije koze kod primjene manje doze, dok je kod primjene veće doze on bio ustanovljen u tri koze. Jedna koza koja je dobila veću dozu pokazivala je tahikardiju s ektopičnim otkucajima od pete do sedme minute nakon indukcije. Apneja se prosječno javljala tijekom prvih 30 sekundi kod primjene manje doze, a tijekom 42 sekunde kod primjene veće doze. U jedne koze apneja je pri primjeni veće doze bila zabilježena tijekom 314 sekundi. Toj je kozi za buđenje dano umjetno disanje nakon 106 sekundi te ponovljeno nakon 296 sekundi. Životinje su pokazivale težak dišni poremećaj s trbušnim disanjem u tijeku prvih nekoliko sekundi. Vrijednosti su se vratile na normalu nakon 15 minuta. Rezultati pokazuju da propofol smanjuje dišnu aktivnost u koza te je nužno primijeniti ventilaciju s pozitivnim tlakom. On ne dovodi do gubitka osjeta boli te treba primijeniti analgetike

Kloniranje, izražajnost i pročišćavanje bjelančevine 28 iz vanjske membrane Salmonelle enterice serovar Typhimurium za razvoj podjediničnog cjepiva - kratko priopćenje

Salmonella Typhimurium, a major gastrointestinal pathogen, poses a global threat to human health. Public health problems associated with this organism have increased to the extent that it has become a major issue. The bacterium is becoming resistant to the commonly available antibiotics, and vaccines also suffer from limitations such as short lived immunity. Therefore, there is an urgent need for the development of an effective vaccine. The outer membrane proteins (Omps) of Salmonella have proven their capability to be developed as a vaccine candidate for prevention of salmonellosis. With this aim, in the present study the Omp28 gene of Salmonella Typhimurium was amplified, cloned and expressed under an IPTG induction system. The recombinant protein thus produced was purified and tested for its antigenicity. The antigenicity of the purified protein was confirmed by western blotting with antiserum raised in rabbit against Omps of S. Typhimurium. The Omp28 gene was amplified as a 330bp product. The expressed protein was found to be of approximately 28kDa and it produced a strong signal in western blot analysis. This study concluded that Omp28 may be proven to be an effective candidate for the development of r-DNA vaccine against salmonellosis.Salmonella Typhimurium glavni je gastrointestinalni patogen koji je globalna prijetnja ljudskome zdravlju. Javnozdravstveni problemi povezani s ovim organizmom povećali su se do te mjere da je postao glavno pitanje na koje se traže brojni odgovori. Bakterija postaje otporna na najčešće dostupne antibiotike, a ograničavajuća uporaba cjepiva povezana je s kratkotrajnim imunitetom. Zbog toga postoji hitna potreba za razvoj učinkovitog cjepiva. Vanjske bjelančevine membrane (engl. Outer membrane proteins, Omps) salmonele dokazale su svoju sposobnost kandidata za razvoj cjepiva koje bi se koristilo u prevenciji salmoneloze. S tim je ciljem u ovom radu, pod uvjetima IPTG indukcijskog sustava, provedeno umnažanje i kloniranje te provjerena izražajnost gena za Omp28 iz Salmonelle Typhimurium. Tako dobivena rekombinantna bjelančevina pročišćena je i testirana s obzirom na antigenu sposobnost. Antigena sposobnost pročišćene bjelančevine potvrđena je uporabom Western blot metode s antiserumom protiv Omps-a iz S. Typhimurium dobivenim od zeca. Genom Omp28 umnožen je kao 330bp produkt. Bjelančevina je imala približno 28 kDa i Western blot analizom pokazala je izraženost jakog signala. Ovim je istraživanjem zaključeno da Omp28 može poslužiti kao učinkoviti kandidat za razvoj r-DNA cjepiva protiv salmoneloze

Eleketroencefalografski pokazatelji za vrijeme anestezije propofolom i ksilazin-ketaminom u koza

The use of intravenous anaesthesia for short term surgical procedures in animal husbandry practices is increasing. However, information on the quality of an anaesthetic regime in goats has remained inadequate. Therefore, electroencephalographic studies were conducted on twelve apparently healthy adult female Barbari crossbred goats, aged 2 to 4 years, to assess the anaesthetic quality of a propofol and xylazine-ketamine combination. Quantitative analysis of EEG parameters [Total power, Median Frequency, Spectral Edge Frequency 90 (SEF-90) and Relative Power (RP) of different frequency bands delta (δ), theta (θ), alpha (α) and beta (β)] were assessed pre-experimentally (control), and at one, five, 10, 30 min, one hr, and two hr after intravenous propofol (4 mg/kg) and xylazine (0.05 mg/kg)-ketamine (4 mg/kg) administration. After propofol and xylazine-ketamine administration total power, RP-δ and θ increased significantly (P<0.05) while SEF 90, MF, RP-α and RP-β decreased. Most of the EEG changes were adequately depicted in vertex and parietal channels. Spectral analysis of EEG tracings suggested that propofol produced minimum anaesthetic stress and is a safer and better choice for short term anaesthesia in goats.U stočarskoj praksi se za kratkotrajne kirurške zahvate sve više primjenjuje intravenska anestezija. Nedostaju međutim podaci na temelju kojih bi se ustanovila kvaliteta anestezijskog protokola u koza. Kako bi se procijenila kvaliteta kombinacije anestetika propofola i ksilazin-ketamina, provedena je analiza elektoencefalografskih pokazatelja u 12 zdravih odraslih koza. Koze su bili križanci barbari pasmine u dobi od 2 do 4 godine. Kvantitativna analiza EEG pokazatelja (total power, median frequency, SEF-90, relative power delta-δ, theta-θ, alfa-α i beta-β frekvencijskih pojaseva) procijenjeni su prije pokusa (kontrolna skupina), te 1, 5, 10, 30 minuta, jedan sat i dva sata nakon intravenske primjene propofola (4 mg/kg) i ksilazin (0,05 mg/kg)-ketamina (4 mg/kg). Nakon primjene propofola i ksilazin-ketamina total power, te relative power-δ i relative power-θ znakovito su porasli (P < 0,05), dok su se SEF 90, median frequency, relative power-α i relative power-β snizili. Većina EEG promjena odgovarajuće je prikazana u verteksu i parijetalnim kanalima. Spektralna analiza EEG-a upućuje na to da propofol u anestezijskom protokolu uzrokuje minimalan stres te je, u usporedbi sa ksilazin-ketaminom, za kratkotrajnu anesteziju koza sigurniji i bolji izbor

Elektroencefalografske promjene kod pokusno uzrokovane boli u koza.

Electroencephalographic (EEG) studies were conducted during experimental pain induction in goats to find the association between routine managemental stress and EEG patterns. Duplicate EEG records from 4 adult (age 8 - 12 months, 10 ± 2 kg body mass) female goats (crossbred Jamunapari and local), using bipolar scalp electrodes were obtained. Pain was induced in a conscious and locally anaesthetised state using a rubber tourniquet applied at the base of the tail and fastened. Xylocaine 2% was used as an injection in the epidural space to achieve local anaesthesia. EEG recordings were taken at 0, 2 and 5 min. after pain application and at the same time intervals after removal of the tourniquet. The EEG frequencies upon pain induction in conscious and epidural anaesthetized states recorded were 38.50 ± 1.96, 33.88 ± 1.42, 31.25 ± 1.39 and 41.88 ± 0.91, 35.63 ± 0.94, 31.50 ± 0.82 Hz at 0, 2 and 5 min of application of pain stimulus, respectively. The frequencies ranged from 26 to 46 Hz in conscious and 27 to 45 Hz in epidural anaesthetized states, whereas amplitudes were higher after 2 min of pain application in both states. With tourniquet removal, the frequency increased significantly (P<0.05) after 2 min in a conscious state, whereas in an epidural anaesthetized state, it increased initially and then declined significantly (P<0.05). The amplitudes and frequencies during pain induction and removal were found to be significantly (P<0.05) different from each other and significantly (P<0.05) higher than in the control (27.75 ± 1.13 Hz and 5.80 ± 0.21μV). Prominent behavioural changes were observed with pain induction. Hence EEG changes can be used as a tool to understand and quantify painful distress in goat.Provedena su elektroencefalografska (EEG) istraživanja kod pokusno izazvane boli u koza sa svrhom da se ustanovi utjecaj stresa uzrokovanoga proizvodnim procesom na elektroencefalogram. Analizirani su rezultati nakon dvokratnoga postupka EEG-a primjenom bipolarnih elektroda na kožu lubanje u četiri odrasle koze (križane Jamunapari i lokalne) u dobi od 8 do 12 mjeseci, tjelesne mase 10 ± 2 kg. Bol je bila izazvana čvrstim stezanjem gumenoga poveza na bazi repa u koza bez anestezije i u koza s epiduralnom anestezijom. Za regionalnu je anesteziju bio upotrijebljen 2 %-tni ksilokain ubrizgan u epiduralni prostor. EEG je bila provedena 0., 2. i 5. minute nakon izazivanja boli te 0., 2. i 5. minute po prestanku bolnoga podražaja. Frekvencija EEG nakon bolnog podražaja u koza bez anestezije iznosila je 38,50 ± 1,96 Hz 0. minute, 33,88 ± 1,42 Hz 2. minute i 31,25 ± 1,39 Hz 5. minute, a u koza s lokalnom anestezijom 41,88 ± 0,91 Hz, 35,63 ± 0,94 Hz i 31,50 ± 0,82 Hz. Frekvencije su se kretale od 26 do 46 Hz u koza bez anestezije, a 27 do 45 Hz u koza s primijenjenom epiduralnom anestezijom, dok su amplitude bile veće nakon 2 minute bolnog podražaja u obje skupine. Frekvencije su se značajno povećale (P<0,05) dvije minute nakon prestanka bolnog podražaja u koza bez lokalne enestezije, dok su se u onih s epiduralnom anestezijom početno značajno povećale, a zatim značajno smanjile. Amplitude i frekvencije za vrijeme i nakon bolnog podražaja bile su međusobno značajno različite, a također i značajno veće nego u kontrolnih koza (27,75 ± 1,13 Hz and 5,80 ± 0,21 μV). Značajne promjene u ponašanju životinja bile su uočene nakon bolnog podražaja. Promjene u elektrokardiogramu mogu se rabiti za proučavanje boli i određivanje jačine boli u koza

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to &lt;90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], &gt;300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of &lt;15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P&lt;0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P&lt;0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Search for new particles in events with energetic jets and large missing transverse momentum in proton-proton collisions at root s=13 TeV

A search is presented for new particles produced at the LHC in proton-proton collisions at root s = 13 TeV, using events with energetic jets and large missing transverse momentum. The analysis is based on a data sample corresponding to an integrated luminosity of 101 fb(-1), collected in 2017-2018 with the CMS detector. Machine learning techniques are used to define separate categories for events with narrow jets from initial-state radiation and events with large-radius jets consistent with a hadronic decay of a W or Z boson. A statistical combination is made with an earlier search based on a data sample of 36 fb(-1), collected in 2016. No significant excess of events is observed with respect to the standard model background expectation determined from control samples in data. The results are interpreted in terms of limits on the branching fraction of an invisible decay of the Higgs boson, as well as constraints on simplified models of dark matter, on first-generation scalar leptoquarks decaying to quarks and neutrinos, and on models with large extra dimensions. Several of the new limits, specifically for spin-1 dark matter mediators, pseudoscalar mediators, colored mediators, and leptoquarks, are the most restrictive to date.Peer reviewe

Combined searches for the production of supersymmetric top quark partners in proton-proton collisions at root s=13 TeV

A combination of searches for top squark pair production using proton-proton collision data at a center-of-mass energy of 13 TeV at the CERN LHC, corresponding to an integrated luminosity of 137 fb(-1) collected by the CMS experiment, is presented. Signatures with at least 2 jets and large missing transverse momentum are categorized into events with 0, 1, or 2 leptons. New results for regions of parameter space where the kinematical properties of top squark pair production and top quark pair production are very similar are presented. Depending on themodel, the combined result excludes a top squarkmass up to 1325 GeV for amassless neutralino, and a neutralinomass up to 700 GeV for a top squarkmass of 1150 GeV. Top squarks with masses from 145 to 295 GeV, for neutralino masses from 0 to 100 GeV, with a mass difference between the top squark and the neutralino in a window of 30 GeV around the mass of the top quark, are excluded for the first time with CMS data. The results of theses searches are also interpreted in an alternative signal model of dark matter production via a spin-0 mediator in association with a top quark pair. Upper limits are set on the cross section for mediator particle masses of up to 420 GeV

Probing effective field theory operators in the associated production of top quarks with a Z boson in multilepton final states at root s=13 TeV

Peer reviewe

MUSiC : a model-unspecific search for new physics in proton-proton collisions at root s=13TeV

Results of the Model Unspecific Search in CMS (MUSiC), using proton-proton collision data recorded at the LHC at a centre-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 35.9 fb(-1), are presented. The MUSiC analysis searches for anomalies that could be signatures of physics beyond the standard model. The analysis is based on the comparison of observed data with the standard model prediction, as determined from simulation, in several hundred final states and multiple kinematic distributions. Events containing at least one electron or muon are classified based on their final state topology, and an automated search algorithm surveys the observed data for deviations from the prediction. The sensitivity of the search is validated using multiple methods. No significant deviations from the predictions have been observed. For a wide range of final state topologies, agreement is found between the data and the standard model simulation. This analysis complements dedicated search analyses by significantly expanding the range of final states covered using a model independent approach with the largest data set to date to probe phase space regions beyond the reach of previous general searches.Peer reviewe

Measurement of prompt open-charm production cross sections in proton-proton collisions at root s=13 TeV

The production cross sections for prompt open-charm mesons in proton-proton collisions at a center-of-mass energy of 13TeV are reported. The measurement is performed using a data sample collected by the CMS experiment corresponding to an integrated luminosity of 29 nb(-1). The differential production cross sections of the D*(+/-), D-+/-, and D-0 ((D) over bar (0)) mesons are presented in ranges of transverse momentum and pseudorapidity 4 < p(T) < 100 GeV and vertical bar eta vertical bar < 2.1, respectively. The results are compared to several theoretical calculations and to previous measurements.Peer reviewe