Towards a tailored approach for patients with acute diverticulitis and abscess formation. The DivAbsc2023 multicentre case-control study.

BACKGROUND: This multicentre case-control study aimed to identify risk factors associated with non-operative treatment failure for patients with CT scan Hinchey Ib-IIb and WSES Ib-IIa diverticular abscesses. METHODS: This study included a cohort of adult patients experiencing their first episode of CT-diagnosed diverticular abscess, all of whom underwent initial non-operative treatment comprising either antibiotics alone or in combination with percutaneous drainage. The cohort was stratified based on the outcome of non-operative treatment, specifically identifying those who required emergency surgical intervention as cases of treatment failure. Multivariable logistic regression analysis to identify independent risk factors associated with the failure of non-operative treatment was employed. RESULTS: Failure of conservative treatment occurred for 116 patients (27.04%). CT scan Hinchey classification IIb (aOR 2.54, 95%CI 1.61;4.01, P < 0.01), tobacco smoking (aOR 2.01, 95%CI 1.24;3.25, P < 0.01), and presence of air bubbles inside the abscess (aOR 1.59, 95%CI 1.00;2.52, P = 0.04) were independent predictors of failure. In the subgroup of patients with abscesses > 5 cm, percutaneous drainage was not associated with the risk of failure or success of the non-operative treatment (aOR 2.78, 95%CI - 0.66;3.70, P = 0.23). CONCLUSIONS: Non-operative treatment is generally effective for diverticular abscesses. Tobacco smoking's role as an independent risk factor for treatment failure underscores the need for targeted behavioural interventions in diverticular disease management. IIb Hinchey diverticulitis patients, particularly young smokers, require vigilant monitoring due to increased risks of treatment failure and septic progression. Further research into the efficacy of image-guided percutaneous drainage should involve randomized, multicentre studies focussing on homogeneous patient groups.

Validation of the Italian version of the Northoff Catatonia Rating Scale.

PURPOSE: Catatonia is a psychomotor syndrome characterized by heterogeneous motor, behavioral and affective alterations, and, in some cases, neurovegetative abnormalities that can be life-threatening. Although the prevalence estimates of catatonia are 10-20% of the hospitalized population, its clinical recognition remains a challenge for most clinicians. Differently from other catatonia rating scales, the Northoff Catatonia Rating Scale (NCRS) also evaluates the affective alterations that patients experience during catatonia and thus provides a more inclusive assessment of the alterations associated with this condition. To provide clinicians with a valuable tool for diagnosis, we translated the NCRS in Italian and validated it on a sample of 52 hospitalized patients with psychiatric disorders. METHODS: An Italian version of the NCRS was prepared using the forward-backwards translation from English and administered to a sample of 52 in-patients (age 46.9±2.37 years). The inter-rater reliability, score correlations, internal coherence and decision statistics were computed. RESULTS: The inter-rater agreement was higher for the motor subscale (100% agreement) than for the behavioral (94%) or affective subscales (92.3%). The inter-rater agreement was 100% for the diagnosis of catatonia. The NCRS correctly identified all patients with catatonia according to DSM-5 (sensitivity= 100%) and had a specificity of 88.9%, and its subscale scores were highly inter-correlated. CONCLUSIONS: This validation shows that the NCRS yields a good accuracy in diagnosing catatonia and high inter-rater reliability. Moreover, the high correlation between its subscales supports the view that catatonia is a multi-faceted truly psycho-motor syndrome. In conclusion, the validation and Italian translation of the NCRS provides the clinicians with a helpful tool for diagnosing catatonia which is easy to use and assesses the full psychomotor complexity of the syndrome.

Photosynthetic properties of spring geophytes assessed by chlorophyll fluorescence analysis.

Since spring ephemerals are credited to be all "sun" species with unusually elevate photosynthesis, in contrast to shade-tolerant trees and understory geophytes with a long aboveground cycle, we examined the photosynthetic efficiency of 6 woody species, 9 long-cycle geophytes, and 8 spring ephemeral geophytes using blue flashes of increasing energy with the Imaging PAM fluorometer. Several parameters were obtained: quantum yield of electron transport (ΦETR) or of PSII (ΦPSII), maximum measured photosynthesis rate (ETRhv), maximum extrapolated rate of photosynthesis (ETRem), half-saturating photon flux density (KPAR), and in some cases photochemical (qP) and non-photochemical quenching (NPQ). Results confirm the ecological consistency of the three plant groups, with internal differences. Woody species have low ETRem and KPAR values with good ΦETR; long-cycle herbs have low ETRem and ΦETR and moderate KPAR values; spring ephemerals have elevate ΦETR, ETRem and KPAR values. The mean ETRem of ephemerals of 91 µmol m-2 s-1 exceeds that of long-cycle herbs 2.9-fold and woody species 4.8-fold, and corresponds to 19 µmol CO2 m-2 s-1 by assuming an ETR/ΦCO2 ratio of 4.7. Highest photosynthesis rates and KPAR were exhibited by five ephemerals (Eranthis, Erythronium, Narcissus, Scilla, Tulipa) with peak ETRem values equivalent to ∼40 µmol CO2 m-2 s-1 or ∼60 µmol CO2 (g Chl)-1 s-1 ("sun" species). According to a new, fluorescence based heliophily index, all trees and five long-cycle herbs were definitely "shade" species, while four long-cycle herbs and three ephemerals were intermediate shade-tolerant.

Lipoxin receptors.

Lipoxins (LXs) represent a class of arachidonic acid (AA) metabolites that carry potent immunoregulatory and anti-inflammatory properties, LXA4 and LXB4 being the main components of this series. LXs are generated by cooperation between 5-lipoxygenase (LO) and 12- or 15-LO during cell-cell interactions or by single cell types. LX epimers at carbon 15, the 15-epi-LXs, are formed by aspirin-acetylated cyclooxygenase-2 (COX-2) in cooperation with 5-LO. 15-epi-LXA4 is also termed aspirin-triggered LX (ATL). In vivo studies with stable LX and ATL analogs have established that these eicosanoids possess potent anti-inflammatory activities. A LXA4 receptor has been cloned. It belongs to the family of chemotactic receptors and clusters with formyl peptide receptors on chromosome 19. Therefore, it was initially denominated formyl peptide receptor like 1 (FPRL1). This receptor binds with high affinity and stereoselectivity LXA4 and ATL. It also recognizes a variety of peptides, synthetic, endogenously generated, or disease associated, but with lower affinity compared to LXA4. For this reason, this receptor has been renamed ALX. This review summarizes the current knowledge on ALX expression, signaling, and potential pathophysiological role. The involvement of additional recognition sites in LX bioactions is also discussed.

Inhibition of protein kinase c-Src reduces the incidence of breast cancer metastases and increases survival in mice: implications for therapy.

c-Src is a proto-oncogene, belonging to the nonreceptor protein kinases family, which plays a prominent role in carcinogenesis. In this study, we tested the hypothesis that c-Src could promote breast cancer metastasis acting on several cell types and that pharmacological disruption of its kinase activity could be beneficial for the treatment of metastases. Female BALB/c-nu/nu mice were subjected to intracardiac injection of the human breast cancer cells MDA-MB-231 (MDA-231), which induced prominent bone and visceral metastases. These were pharmacologically reduced by treatment with the c-Src inhibitor [7-{4-[2-(2-methoxy-ethylamino-ethoxy]-phenyl}-5-(3-methoxy-phenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine] CGP76030 (100 mg/kg/day p.o.), resulting in decreased morbidity and lethality. Metastases were more severe in mice injected with MDA-231 cells stably transfected with wild-type c-Src (MDA-231-SrcWT), whereas transfection in injected cells of a c-Src kinase-dead dominant-negative construct (MDA-231-SrcDN) resulted in reduced morbidity, lethality, and incidence of metastases similar to the mice treated with the inhibitor. An analogous beneficial effect of c-Src inhibition was observed in subcutaneous and intratibial implanted tumors. In vitro, c-Src suppression reduced MDA-231 cell aggressiveness. It also impaired osteoclast bone resorption both directly and by reducing expression by osteoblasts of the osteoclastogenic cytokines interleukin-1beta and interleukin-6, whereas parathyroid hormone-related peptide was not implicated. c-Src was also modestly but consistently involved in the enhancement of endothelial cell proliferation in vitro and angiogenesis in vivo. In conclusion, we propose that c-Src disruption affects the metastatic process and thus is a therapeutic target for the treatment of breast cancer.

Reduction of c-Src activity by substituted 5,7-diphenyl-pyrrolo[2,3-d]-pyrimidines induces osteoclast apoptosis in vivo and in vitro. Involvement of ERK1/2 pathway.

We employed potent and selective c-Src inhibitors to investigate the functional and molecular consequences of inhibited c-Src tyrosine kinase activity in osteoclasts. These pyrrolopyrimidine derivatives reduced osteoclast numbers and induced osteoclast disruption in vivo. In vitro, they inhibited resorption pit formation and osteoclastogenesis, impaired adhesion ability and actin ring organization, and induced programmed cell death in mature osteoclasts. The cell death receptor Fas and p53 were insensitive to c-Src modulation. The expression of the cyclin-dependent kinase (CDK)-inhibitor p21WAF1/CIP1 was markedly reduced, but neither Bcl-2 nor Bcl-xL or Bax were modulated by c-Src inhibition. Caspase-9, and to a lesser extent caspase-3, but not caspase-8, were transiently cleaved (activated) by treatment with the c-Src inhibitors. c-Src inhibition stabilized p38 mitogen-activated protein kinase (MAPK), whereas the c-Jun N-terminal kinase (JNK) pathway did not appear to be modulated by our compounds. Most interestingly, transient extracellular signal regulated kinase (ERK1/2) dephosphorylation followed by sustained remarkable rephosphorylation overwhelming control levels was observed in response to c-Src inhibition. Blockade of ERK1/2 rephosphorylation by PD98059 reduced osteoclast nuclear disruption, suggesting the involvement of this pathway in apoptosis. Collectively, these data demonstrate that small pyrrolopyrimidine derivatives impair osteoclast function and induce cell damage suggestive of apoptosis in vivo and in vitro, with mechanisms presumably involving selective sustained ERK1/2 phosphorylation.

Genotype-phenotype relationship in human ATP6i-dependent autosomal recessive osteopetrosis.

Autosomal-recessive osteopetrosis is a severe genetic disease caused by osteoclast failure. Approximately 50% of the patients harbor mutations of the ATP6i gene, encoding for the osteoclast-specific a3 subunit of V-ATPase. We found inactivating ATP6i mutations in four patients, and three of these were novel. Patients shared macrocephaly, growth retardation and optic nerve alteration, osteosclerotic and endobone patterns, and high alkaline phosphatase and parathyroid hormone levels. Bone biopsies revealed primary spongiosa lined with active osteoblasts and high numbers of tartrate-resistant acid phosphatase (TRAP)-positive, a3 subunit-negative, morphologically unremarkable osteoclasts, some of which located in shallow Howship lacunae. Scarce hematopoietic cells and abundant fibrous tissue containing TRAP-positive putative osteoclast precursors were noted. In vitro osteoclasts were a3-negative, morphologically normal, with prominent clear zones and actin rings, and TRAP activity more elevated than in control patients. Podosomes, alphaVbeta3 receptor, c-Src, and PYK2 were unremarkable. Consistent with the finding in the bone biopsies, these cells excavated pits faintly stained with toluidine blue, indicating inefficient bone resorption. Bone marrow transplantation was successful in all patients, and posttransplant osteoclasts showed rescue of a3 subunit immunoreactivity.