Predictive Performance of Serum S100B Versus LDH in Melanoma Patients: a Systematic Review and Meta-Analysis

Currently, no consensus on the use of blood tests for monitoring disease recurrence in patients with resected melanoma exists. The only meta-analysis conducted in 2008 found that elevated serum S100B levels were associated with significantly worse survival in melanoma patients. Serum LDH is an established prognostic factor in patients with advanced melanoma.To compare the discriminative and prognostic ability of serum S100B with that of serum LDH in patients with melanoma.This systematic review and meta-analysis were reported in accordance with the PRISMA Statement. The study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD42019137138).A quantitative analysis of data from 6 eligible studies included 1,033 patients with cutaneous melanoma. The discriminative ability of serum S100B at identifying disease relapse [pooled Area Under the ROC (AUROC) 78.64 (95% CI 70.28; 87.01)] was significantly greater than the discriminative ability of serum LDH [AUROC 64.41 (95% CI 56.05; 7278)] (p=0.013). Ten eligible studies with 1,987 patients were included in the risk of death analysis. The prognostic performance of serum S100B [pooled estimate of adjusted hazard ratio (HR) 1.78 (95% CI 1.38; 2.29)] was independent but not superior to that of serum LDH [HR 1.60 (95% CI 1.36; 2.29)].A relatively small number of articles were eligible and there was considerable heterogeneity across the included studies.Serum biomarkers may provide relevant information on melanoma patient status and should be further researched. Serum S100B is a valid marker for diagnosis of melanoma recurrence.The study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD42019137138)

Lactose intolerance but not lactose maldigestion is more frequent in patients with irritable bowel syndrome than in healthy controls : A meta-analysis

Irritable bowel syndrome (IBS) affects 10%-20% of the adult population and is characterized by abdominal symptoms without relevant organic disease. There are numerous clinical trials available investigating the relationship between IBS, lactose maldigestion (LM), and lactose intolerance (LI), but there have been no meta-analyses on this topic yet. We aimed to assess the prevalence of LM, objective and subjective (self-reported) LI in IBS patients compared to healthy controls (HC) without IBS.A systematic literature search was conducted up to 24 April 2018 in PubMed, Embase, and Cochrane Library. Adult IBS patients had to be diagnosed according to the Rome criteria or other well-defined criteria system. We enrolled controlled studies including healthy adult participants without IBS, as control group. Odds ratios with 95% confidence intervals were calculated.Altogether 14 articles were suitable for statistical analyses. IBS patients reported themselves significantly more frequently lactose intolerant than HCs (odds ratio [OR] = 3.499; 95% confidence interval [CI] = 1.622-7.551). Generally, there was no significant difference in the prevalence of LM based on ingested lactose dose (OR = 1.122; 95% CI = 0.929-1.356) and test type (OR = 1.156; 95% CI = 0.985-1.356). However, significantly more IBS patients had objective LI (OR = 2.521; 95% CI = 1.280-4.965).Lactose intolerance, but not LM is more frequent among patients with IBS compared to HCs. According to our results, IBS among other functional bowel disorders is a possible contributing factor of LI in people with LM

Phosphorylation adjacent to the nuclear localization signal of human dUTPase abolishes nuclear import: Structural and mechanistic insights

Phosphorylation adjacent to nuclear localization signals (NLSs) is involved in the regulation of nucleocytoplasmic transport. The nuclear isoform of human dUTPase, an enzyme that is essential for genomic integrity, has been shown to be phosphorylated on a serine residue (Ser11) in the vicinity of its nuclear localization signal; however, the effect of this phosphorylation is not yet known. To investigate this issue, an integrated set of structural, molecular and cell biological methods were employed. It is shown that NLS-adjacent phosphorylation of dUTPase occurs during the M phase of the cell cycle. Comparison of the cellular distribution of wild-type dUTPase with those of hyperphosphorylation- and hypophosphorylation-mimicking mutants suggests that phosphorylation at Ser11 leads to the exclusion of dUTPase from the nucleus. Isothermal titration microcalorimetry and additional independent biophysical techniques show that the interaction between dUTPase and importin-alpha, the karyopherin molecule responsible for 'classical' NLS binding, is weakened significantly in the case of the S11E hyperphosphorylation-mimicking mutant. The structures of the importin-alpha-wild-type and the importin-alpha-hyperphosphorylation-mimicking dUTPase NLS complexes provide structural insights into the molecular details of this regulation. The data indicate that the posttranslational modification of dUTPase during the cell cycle may modulate the nuclear availability of this enzyme

Effect of metritis on the reproductive performance of dairy cows

Az involúció során a méh baktériumos fertőzései és az abból kialakuló gyulladásos megbetegedések rendkívüli mértékben rontják a tejelő tehenek szaporodási teljesítményét. Ezért a kóroktan és kórfejlődés pontosabb megismerése, a diagnosztika fejlődése nagy gyakorlati és gazdasági jelentőségű. Doktori értekezésem elkészítéséhez szükséges kísérleteket magyarországi nagyüzemi tejelő tehenészetekben hajtottuk végre, négy kísérlet sorozatban, több éven keresztül. A PM kialakulásában szerepet játszó hajlamosító és befolyásoló, illetve a diagnosztizálását elősegítő tényezők fennállása esetén a betegség előfordulási aránya nő. A PM kockázata általában szignifikánsan nő ellés során a szülőútban végzett manuális beavatkozás, MBV, ketonuriában és/vagy hiperketonémiában megnyilvánuló energiahiányos állapot esetén, és jelzi a betegség jelentkezését, ha a testhőmérséklet a 3-5. pp napok között nő. A tPM nagyobb arányú előfordulását valószínűsíti, ha a fentieken túl az állat előző laktációs tejtermelése 9400 liter feletti, legalább 3+-es ketonuria, illetve utal a tPM jelentkezésére a pp 3-5. napján a testhőmérséklet emelkedése mellett a tejtermelés csökkenése is. Eredményeink segítségével a nagy létszámú tejelő tehenészetekben pontosabban szervezhetők meg a megbetegedés felismerése szempontjából meghatározó jelentőségű ellés utáni szűrővizsgálatok, ami lehetővé teszi a metritisek időbeni diagnosztizálását, amitől a terápiás beavatkozások nagyobb hatékonysága illetve a betegségek negatív gazdasági hatásainak csökkentése remélhető. Feltártuk a puerperális metritis illetve egyéb involúciós betegségek közötti kapcsolatot. Vizsgálataink alapján reális kép alkotható a PM tejtermeléssel fennálló összefüggéséről, illetve a szaporodásbiológiai teljesítményre gyakorolt negatív hatásáról. Meghatároztuk a fontosabb méhpatogének MIC értékét, a GN anaerobok esetén ezt először tettük meg Magyarországon gyűjtött méhtampon mintákból kitenyésztett baktériumtörzsekkel. A fontosabb uterinális patogén baktériumok érzékenysége csökken az oxitetraciklinre és az amoxicillinre (nő a MIC értéke). A cefapirinre az E. coli kivételével az összes méhpatogén érzékeny. A cefquinomra valamennyi méhpatogén megfelelő érzékenységet mutatott in vitro vizsgálatainkban (alacsony MIC értékek). Az energetikai egyensúly-hiány ketonuriában megnyilvánuló dekompenzációja és az involúciós szövődmények lefolyása között összefüggést mutatnak eredményeink. Megállapítottuk, hogy antiketogenikus kezeléssel javítható az iu. antimikrobiális kezelések hatékonysága, következésképpen csökkenthetők a PM-hez társuló szaporodásbiológia zavarok és az ebből származó gazdasági veszteségek. A PM kezelések során a nagy dózisú OTC alkalmazása után kevesebb A. pyogenest tenyésztettünk ki pp 5. hetén vett méhtamponokból, és magasabb volt a vemhesülési arány is, de ez az alkalmazási mód magas élelmiszerbiztonsági kockázattal jár, ezért nem javasoljuk. Az ellés utáni 4-5. héten az A. pyogenes jelenléte a méhben hátrányosan befolyásolja a vemhesülést. Ezért a méh bakteriológiai állapotának felmérésére az ellés utáni 5. héten elegendő ennek a kórokozónak a kimutatása. Ehhez kapcsolódóan megállapítottuk, hogy az A. pyogenes ellen is hatékony antimikrobiális szer alkalmazása szignifikánsan növelte a vemhesülést. A vizsgálataink során pontos képet alkothattunk az egyes, elterjedten használt gyógykezelési eljárások hatékonyságáról, és az azt befolyásoló néhány tényezőről. Mindezek az ismeretek az állattenyésztői, állatorvosi gyakorlat számára egyaránt jól hasznosíthatóak. Eredményeink elősegíthetik tejelő tehenészetekben az ellés utáni időszakban a klinikai ellenőrző vizsgálatok szervezését, az involúció bakteriális szövődményeinek mielőbbi felismerését, gyógykezelését. Mindezzel a tehenek ellés utáni mielőbbi újravemhesülését szolgálva, ami a két ellés közötti idő rövidítését eredményezve a gazdaságos tejtermelés záloga. Bacterial infections of postpartum uterus during the involution period and their clinical manifestations i.e. different types of metritis have detrimental effects on reproductive performance of dairy cows. Therefore, more precise knowledge on their aetiology and pathogenesis as well as the improvement of diagnostic tools has of great practical and economical importance. The data presented in this doctoral thesis are obtained from four series of field trials performed in large scale dairy herds in Hungary during the past few years. Presence of certain predisposing and influencing factors together with early indicator symptoms are good predictor of the disease. Risk of PM is significantly higher, when manual intervention during calving and/or RFM and/or NEB characterized by ketonuria or hyperketonaemia is present, while elevation of rectal temperature between pp days 3-5 is the indicator of the disease. TPM occurs more frequently, when, beside the above mentioned factors, milk yield at the previous lactation was >9400 l and milk yield between pp days 3-5 is decreased. By means of our results the post partum monitoring of cows on large scale dairy farms can be better organized, which enhances the timely diagnosis of PM and may result in a more efficacious therapy and consequently, decreasing of economic losses due to the disease. We also exhibited the relationship between PM and other diseases of involution. By means of our observations a realistic estimation can be made on the relationship of PM with milk yield and its detrimental effect on reproduction performance. MIC of primary uterine pathogens was determined in a series of trials. For Gram Negative anaerobic strains from bovine uterus, our results are the first ones obtained in Hungary. We revealed that sensitivity of aerobic primary uterine pathogens has been decreased for traditionally used oxytetracyclin and amoxicillin (increasing MIC). All primary uterine pathogens, except E.coli, were, however, sensitive for cephapyrin. Cefquinome proved to be highly efficacious, in vitro, against all uterine pathogens (low MIC). Decompensated NEB, characterized by ketonuria had a significant impact on the course of involution in animals with PM. It means that if NEB is compensated by using an antiketogenic treatment, the efficacy of IU treatment of PM is increased, and consequently the economic losses caused by the poorer reproduction performance of the cows with PM can be reduced. For the therapy of PM, a high dose (3 g/day) of OTC treatment proved to be more efficacious than amoxicillin and gentamycin in terms of lower frequency of EM as well as lower incidence of A. pyogenes as primary uterine pathogen at pp week 5th . Statistically significant difference were found also in higher fertility rate and shorter service period. Presence of A. pyogenes at pp week 5th in the uterus has of significant negative effect on reproduction performance, regardless of treatment, as compared to A. pyogenes free animals. Therefore we concluded that detection of this species is enough for monitoring of uterine bacteriological status. We also demonstrated that antimicrobial therapy effective against A. pyogenes significantly improves fertility rate. Our results can be applied very well in the daily routine of dairy farming. By using them, monitoring examinations can be better organized, timely diagnosis is facilitated, consequently recognition and treatment of bacterial complications of involution will be more effective and reproduction performance will be better, which is an important prerequisite for the economical milk production.N

Drogrehabilitáció. Az elmúlt tíz év nagyobb szakmai és társadalompolitikai változásai és azok hatásai egy drogrehabilitációs intzézetre

régi képzésSzociálpolitika szak levelezőB

Progesterone profiles and oestrous cycle changes following superovulatory treatment of Holstein-Friesian dairy cows in a tropical environment

Changes of progesterone (P4) profiles and oestrous cycle were investigated up to 70 days in 20 superovulated Holstein-Friesian cows in a dry tropical environment (Brazil). Superovulated cows showed no significant differences in relation to P4 level at the time of embryo recovery (39.0 ± 27.1 nmol/L, P = 0.536), first and second (12.0 ± 6.0 and 10.7 ± 2.2 nmol/L, P = 0.543) cycle. There was a close correlation between serum P4 concentration and the number of corpora lutea (CL; 13.3 ± 9.5) at the recovery (P < 0.0001). After the embryo collection, cows returned to cycle in different ways: (i) group of donors returning to cycle after 2.2 ± 0.8 days, (ii) group with a delay of 11.0 ± 1.9 days; and (iii) animals having a long (28.8 ± 2.2 days) acyclic period, which is significant (P < 0.001). The remaining animals (30%) showed cystic ovarian malformations. P4 level at the time of embryo recovery does not influence the oestrous cycle changes. The results suggest that Holstein-Friesian donor cows may suffer from cystic ovarian degeneration and may have a long acyclic period after superovulatory treatment in a tropical climate