АБСТИНЕНЦІЯ У ВИХОВНІЙ ДІЯЛЬНОСТІ І ПОГЛЯДАХ МЕЧИСЛАВА KУЗНОВІЧА (1874 – 1945)

Father Mieczysław Kuznowicz (1874 – 1945) was a famous Polish social and educational activist and a patron to artisan and working youths. It was for them that he decided to direct an organization called «St. Stanisław Kostka Artisan and Industrial Youth Association». The aim of the article is to present the ideas and activity of Father Kuznowicz in the field of abstinence.Ксендз Мечислав Kузнович (1874 – 1945) – известный польский общественный и образовательный деятель, наставник ремесничей и рабочей молодежи. С мнением о заброшенной в воспитательном значении молодежи, возглавил организацию «Союз ремесничей и промышленной молодежи, преданной св. Станислава Костко». В статье отражена деятельность и взгляды М. Kузновича на абстинентну (антиалкогольную и антитабачную) позицию среди членов этой организации.Ксьондз Мечислав Kузновіч (1874 – 1945) – відомий польський громадський і освітній діяч, наставник ремісничої і робітничої молоді. З думкою про занедбану у виховному значенні молодь, очолив організацію «Союз ремісничої і промислової молоді, відданій св. Станіслава Костко». У статті висвітлено діяльність і погляди М. Kузновіча на абстиненту (антиалкогольну і антитютюнову) позицію серед членів цієї організації

Methoden zur Berechnung von CSR als Erweiterungsbestandteil des Unternehmenswertes

Das Thema Unternehmensbewertung wurde schon oft durch verschiedenste Einrichtungen (Controlling, Finanzwirtschaft, Rechnungswesen) erforscht. Die Anlässe zur Bewertung können unterschiedlichste Natur haben. Sehr oft geht es bei solchen Bewertungen um Investitionsentscheidungen. Die oberste Zielvorstellung dabei ist es, ein möglichst vollständiges Bild über das Unternehmen in der Gegenwart und über seine Entwicklung in der Zukunft zu erhalten. Die Berücksichtigung rein finanzieller Größen reicht nicht mehr aus, um dieses Bild zu erstellen. Ausgehend von diesen Überlegungen wurde versucht durch diese Arbeit die Methoden zu analysieren, mit denen CSR in die Unternehmensbewertung integriert werden kann. Die Einbeziehung von CSR in den Unternehmenswert ist erst durch die Studie von Orlitzky/Schmidt/Rynes möglich geworden. Die Meta- Analyse (Studie) beweist den Einfluss der Corporate Social Performace (CSP) auf die Corporate Financial Performance (CFP) und vice versa. Als nächstes wurde versucht, geeignete Kriterien zu finden, die einen Vergleiche der Methoden zur Berechnung von CSR ermöglichen. Für diese Zwecke wurden drei Kriterien der Frankfurt-Hohenheim Leitfaden (FHL) von Hoffmann/Ott/Scherhorn herangezogen. Das sind: Naturverträglichkeit, Sozialverträglichkeit und Kulturverträglichkeit. Als viertes Kriterium wurde „Investitionsentscheidung“ als Instrument für Investitionsentscheidungen festgelegt. Das bedeutet wie geeignet oder weniger geeignet ist eine Methode zur Berechnung eines CSR- orientierten Unternehmenswertes für einen Investor. Abschließend wurde versucht die erforschten Methoden anhand dieser Kriterien miteinander zu vergleichen

73. Concurrent weekly cisplatin and radiotherapy in cervical cancer patients. A report on acute toxicity

Material and methodBetween May 1999 and January 2001, 41 consecutive cervical cancer patients (pts), median age 46 yrs (range 29–68), were treated with concurrent cisplatin and pelvic irradiation with curative intent (29 pts FIGO stage IB “bulky”, IIB–IVA) or postoperatively (11 pts who had positive pelvic lymph nodes and/or involvement of the surgical margin and/or large and deeply invasive lesion). Adequate bone marrow function and normal serum creatinine were required. Cisplatin given as a 60-minute infusion, was administered weekly at the dose of 40 mg/sqm (max. 70 mg) for six cycles. Antiemetic therapy was routinely given. Three patients received irradiation on out-patient basis.ResultsA total of 145 cycles were administered. The median number of cisplatin cycles was 4 (range: 1–6). Overall, 65% of pts received at least four cycles of cisplatin. The reasons for chemotherapy discontinuation included low level of creatinine clearence (2 pts), worsening of performance status (3 pts), and myoclonia after cisplatin injection (1 pt). Moderate emesis occurred in one patient, grade 2 leukopenia in two other cases. There were no severe acute effects precluding the delivery of planned radiotherapy. At present six patients are still on therapy.ConclusionPelvic radiotherapy combined with weekly cisplatin is feasible in a routine practice. This modality is also suitable for patients treated on out-patient basis

Effects of an outpatient service holistic rehabilitation program in a case of pulmonary atresia.

A 42-year-old woman affected by pulmonary atresia came to our attention complaining of dyspnea and fatigue for minimal efforts with important desaturation. After assessing her basal functional capacity with a cardiopulmonary exercise test, the patient was enrolled in an extremely individualized rehabilitation program, which entailed a discreet improvement in the quality of life indices, in the absence of side effects. This paper shows that even patients with extremely severe forms of congenital heart disease, when clinical stable, can undergone a tailored cardiorespiratory rehabilitation program. This must be carried out in a monitored environment and under the supervision of expert personnel

Chk1 inhibits replication factory activation but allows dormant origin firing in existing factories

Replication origins are licensed by loading MCM2-7 hexamers before entry into S phase. However, only ∼10% of licensed origins are normally used in S phase, with the others remaining dormant. When fork progression is inhibited, dormant origins initiate nearby to ensure that all of the DNA is eventually replicated. In apparent contrast, replicative stress activates ataxia telangiectasia and rad-3–related (ATR) and Chk1 checkpoint kinases that inhibit origin firing. In this study, we show that at low levels of replication stress, ATR/Chk1 predominantly suppresses origin initiation by inhibiting the activation of new replication factories, thereby reducing the number of active factories. At the same time, inhibition of replication fork progression allows dormant origins to initiate within existing replication factories. The inhibition of new factory activation by ATR/Chk1 therefore redirects replication toward active factories where forks are inhibited and away from regions that have yet to start replication. This minimizes the deleterious consequences of fork stalling and prevents similar problems from arising in unreplicated regions of the genome

Blood basophils from cystic fibrosis patients with allergic bronchopulmonary aspergillosis are primed and hyper-responsive to stimulation by aspergillus allergens

AbstractIntroductionFifteen to sixty percent of cystic fibrosis patients harbor Aspergillus fumigatus (Af) in their airways (CF-AC) and some will develop allergic bronchopulmonary aspergillosis (CF-ABPA). Since basophils play a key role in allergy, we hypothesized that they would display alterations in CF-ABPA patients compared to CF-AC or patients without Af colonization (CF).MethodsUsing flow cytometry, we measured CD203c, CD63 and CD123 levels on basophils from CF-ABPA (N=11), CF-AC (N=14), and CF (N=12) patients before and after ex vivo stimulation with Af allergens.ResultsBaseline CD203c was increased in basophils from CF-ABPA compared to CF-AC and CF patients. Af extract and recombinant Aspf1 stimulated basophils from CF-ABPA patients to markedly upregulate CD203c, along with modest upregulation of CD63 and a CD123 downward trend. Plasma TARC/CCL17 at baseline and post-stimulation cell supernatant histamine levels were similar in the three groups.ConclusionsIn CF-ABPA, blood basophils are primed and hyperresponsive to Af allergen stimulation

Spatial competition constrains resistance to targeted cancer therapy

Adaptive therapy (AT) aims to control tumour burden by maintaining therapy-sensitive cells to exploit their competition with resistant cells. This relies on the assumption that resistant cells have impaired cellular fitness. Here, using a model of resistance to a pharmacological cyclin-dependent kinase inhibitor (CDKi), we show that this assumption is valid when competition between cells is spatially structured. We generate CDKi-resistant cancer cells and find that they have reduced proliferative fitness and stably rewired cell cycle control pathways. Low-dose CDKi outperforms high-dose CDKi in controlling tumour burden and resistance in tumour spheroids, but not in monolayer culture. Mathematical modelling indicates that tumour spatial structure amplifies the fitness penalty of resistant cells, and identifies their relative fitness as a critical determinant of the clinical benefit of AT. Our results justify further investigation of AT with kinase inhibitors

Replication factory activation can be decoupled from the replication timing program by modulating Cdk levels

In the metazoan replication timing program, clusters of replication origins located in different subchromosomal domains fire at different times during S phase. We have used Xenopus laevis egg extracts to drive an accelerated replication timing program in mammalian nuclei. Although replicative stress caused checkpoint-induced slowing of the timing program, inhibition of checkpoint kinases in an unperturbed S phase did not accelerate it. Lowering cyclin-dependent kinase (Cdk) activity slowed both replication rate and progression through the timing program, whereas raising Cdk activity increased them. Surprisingly, modest alteration of Cdk activity changed the amount of DNA synthesized during different stages of the timing program. This was associated with a change in the number of active replication factories, whereas the distribution of origins within active factories remained relatively normal. The ability of Cdks to differentially effect replication initiation, factory activation, and progression through the timing program provides new insights into the way that chromosomal DNA replication is organized during S phase

Plasma anandamide concentrations are lower in children with autism spectrum disorder

Background: Autism spectrum disorder (ASD) is a neurodevelopmentaldisorder characterized by restricted, stereotyped behaviors and impairments in social communication. Although the underlying biological mechanisms of ASD remain poorly understood, recent preclinical research has implicated the endogenous cannabinoid (or endocannabinoid), anandamide, as a significant neuromodulator in rodent models of ASD. Despite this promising preclinical evidence, no clinical studies to date have tested whether endocannabinoids are dysregulated in individuals with ASD. Here, we addressed this critical gap in knowledge by optimizing liquid chromatography-tandem mass spectrometry methodology to quantitatively analyze anandamide concentrations in banked blood samples collected from a cohort of children withand without ASD (N= 112). Findings: Anandamide concentrations significantly differentiated ASD cases (N= 59) from controls (N= 53), such that children with lower anandamide concentrations were more likely to have ASD (p= 0.041). In keeping with this notion, anandamide concentrations were also significantly lower in ASD compared to control children (p= 0.034). Conclusions: These findings are the first empirical human data to translate preclinical rodent findings to confirm a link between plasma anandamide concentrations in children with ASD. Although preliminary, these data suggest that impaired anandamide signaling may be involved in the pathophysiology of ASD