Utero-cervical angle to predict the risk of spontaneous preterm birth: a review of literature.

BACKGROUND: The aim of this paper was to evaluate the predictive role of the uterocervical angle (UCA) in spontaneous preterm birth (sPTB). METHODS: A systematic review of the literature was performed including all studies reporting the association between UCA and sPTB. Searches were performed with the use of a combination of keywords: "cervical length," "uterocervical angle," and "preterm birth" from inception of each database to March 2022. The statistical evaluations were carried out using the Comprehensive Meta-Analysis version 3 (Biostat Inc. USA). RESULTS: Sixteen studies all conducted on the second trimester UCA as well as its association with sPTB were included in this study. In all studies the measurements of cervical length (CL) and UCA were performer in the second trimester, except in one that in the third trimester. In most studies the CL is greater than 30 mm and the UCA is greater than 110 °. In seven studies women with symptoms were considered while in 8 studies the women were asymptomatic. CONCLUSIONS: It is too early for it to reach a firm conclusion on UCA utilization in clinical settings. A higher UCA measurement (greater than 150°) is an important risk factor for deliveries before 37 weeks' gestation. It provides a higher diagnostic performance in high risk patients than the CL measurement. However, the most relevant ultrasound parameter for the prediction of delivery within the next few data in women with preterm delivery remains the cervical length. There is a need to consider both markers and create protocols so that the values obtained with UCA and those with CL can make a real contribution to decisions to be made rather than using only CL.

The unpredictable clinical course of an abdominal cyst diagnosed in the prenatal period: A case report.

Enteric duplication cysts are rare congenital malformations of the gastrointestinal tract. Prenatal diagnosis can be achieved through ultrasound, which may reveal a cystic mass, though the differential diagnosis is broad. We report a case in which the prenatal ultrasound detection of an abdominal cystic mass prompted postnatal magnetic resonance imaging, leading to the diagnosis of an enteric duplication cyst. At 6 weeks of age, the infant developed an obstruction of the small bowel, requiring urgent surgical intervention. This case underscores the difficulties in differentiating abdominal cysts prenatally. Thorough prenatal and neonatal follow-up is crucial, and postnatal magnetic resonance imaging is sometimes essential for accurate diagnosis. The clinical course can be unpredictable, and complications that may arise could necessitate urgent surgical treatment.

Enhanced toxicity of silver nanoparticles in transgenic Caenorhabditis elegans expressing amyloidogenic proteins.

The increasing number of applications of silver nanoparticles (AgNP) prompted us to assess their toxicity in vivo. We have investigated their effects on wild type and transgenic Caenorhabditis elegans (C. elegans) strains expressing two prototypic amyloidogenic proteins: ß2-microglobulin and Aß peptide3-42. The use of C. elegans allowed us to highlight AgNP toxicity in the early phase of the worm's life cycle (LC50 survival, 0.9 µg/ml). A comparative analysis of LC50 values revealed that our nematode strains were more sensitive to assess AgNP toxicity than the cell lines, classically used in toxicity tests. Movement and superoxide production in the adult population were significantly affected by exposure to AgNP; the transgenic strains were more affected than the wild type worms. Our screening approach could be applied to other types of nanomaterials that can enter the body and express any nanostructure-related bioactivities. We propose that C. elegans reproducing the molecular events associated with protein misfolding diseases, e.g. Alzheimer's disease and systemic amyloidosis, may help to investigate the specific toxicity of a range of potentially harmful molecules. Our study suggests that transgenic C. elegans may be used to predict the effect of chemicals in a "fragile population", where an underlying pathologic state may amplify their toxicity.

Assessment of cellular responses after short- and long-term exposure to silver nanoparticles in human neuroblastoma (SH-SY5Y) and astrocytoma (D384) cells.

Silver nanoparticle (AgNP, 20 nm) neurotoxicity was evaluated by an integrated in vitro testing protocol employing human cerebral (SH-SY5Y and D384) cell lines. Cellular response after short-term (4-48 h, 1-100 µ g/ml) and prolonged exposure (up to 10 days, 0.5-50 µ g/ml) to AgNP was assessed by MTT, calcein-AM/PI, clonogenic tests. Pulmonary A549 cells were employed for data comparison along with silver nitrate as metal ionic form. Short-term data: (i) AgNP produced dose- and time-dependent mitochondrial metabolism changes and cell membrane damage (effects starting at 25 µ g/ml after 4 h: EC50s were 40.7 ± 2.0 and 49.5 ± 2.1 µ g/ml for SH-SY5Y and D384, respectively). A549 were less vulnerable; (ii) AgNP doses of ≤ 18 µ g/ml were noncytotoxic; (iii) AgNO3 induced more pronounced effects compared to AgNP on cerebral cells. Long-term data: (i) low AgNP doses (≤ 1 µ g/ml) compromised proliferative capacity of all cell types (cell sensibility: SHSY5Y > A549 > D384). Colony number decrease in SH-SY5Y and D384 was 50% and 25%, respectively, at 1 µ g/ml, and lower dose (0.5 µ g/ml) was significantly effective towards SH-SY5Y and pulmonary cells; (ii) cell proliferation activity was more affected by AgNO3 than AgNPs. In summary, AgNP-induced cytotoxic effects after short-term and prolonged exposure (even at low doses) were evidenced regardless of cell model types.

In vitro toxicity evaluation of engineered cadmium-coated silica nanoparticles on human pulmonary cells.

Cytotoxicity of cadmium-containing silica nanoparticles Cd-SiO2NPs (0.05-100 µg/mL) versus SiO2NPs and CdCl2 was evaluated by an in vitro test battery in A549 by assessing (i) mitochondrial function, (ii) membrane integrity/cell morphology, (iii) cell growth/proliferation, (iv) apoptotic pathway, (v) oxidative stress, after short- (24-48 h) and long-term (10 days) exposure. Both Cd-SiO2NPs and CdCl2 produced dose-dependent cytotoxic effects: (i) MTT-assay: similar cytotoxicity pattern was observed at both 24 and 48 h, with a more Cd-SiO2NPs pronounced effect than CdCl2. Cd-SiO2NPs induced mortality (about 50%) at 1 µ g/mL, CdCl2 at 25 µ g/mL; (ii) calcein-AM/PI staining: decrease in cell viability, noticeable at 25 µ g/mL, enhanced markedly at 50 and 100 µ g/mL, after 24 h. Cd-SiO2NPs induced higher mortality than CdCl2 (25% versus 4%, resp., at 25 µ g/mL) with further exacerbation after 48h; (iii) clonogenic assay: exposure for longer period (10 days) compromised the A549 proliferative capacity at very low dose (0.05 µ g/mL); (iv) a progressive activation of caspase-3 immunolabelling was detected already at 1 µ g/mL; (v) GSH intracellular level was modified by all compounds. In summary, in vitro data demonstrated that both Cd-SiO2NPs and CdCl2 affected all investigated endpoints, more markedly after Cd-SiO2NPs, while SiO2NPs influenced GSH only.

Safety evaluation of engineered nanomaterials for health risk assessment: an experimental tiered testing approach using pristine and functionalized carbon nanotubes.

Increasing application of engineered nanomaterials within occupational, environmental, and consumer settings has raised the levels of public concern regarding possible adverse effects on human health. We applied a tiered testing strategy including (i) a first in vitro stage to investigate general toxicity endpoints, followed by (ii) a focused in vivo experiment. Cytotoxicity of laboratory-made functionalized multiwalled carbon nanotubes (CNTs) (i.e., MW-COOH and MW-NH2), compared to pristine MWCNTs, carbon black, and silica, has been assessed in human A549 pneumocytes by MTT assay and calcein/propidium iodide (PI) staining. Purity and physicochemical properties of the test nanomaterials were also determined. Subsequently, pulmonary toxic effects were assessed in rats, 16 days after MWCNTs i.t. administration (1 mg/kg b.w.), investigating lung histopathology and monitoring several markers of lung toxicity, inflammation, and fibrosis. In vitro data: calcein/PI test indicated no cell viability loss after all CNTs treatment; MTT assay showed false positive cytotoxic response, occurring not dose dependently at exceedingly low CNT concentrations (1 µ g/mL). In vivo results demonstrated a general pulmonary toxicity coupled with inflammatory response, without overt signs of fibrosis and granuloma formation, irrespective of nanotube functionalization. This multitiered approach contributed to clarifying the CNT toxicity mechanisms improving the overall understanding of the possible adverse outcomes resulting from CNT exposure.

Pulmonary toxicity of instilled cadmium-doped silica nanoparticles during acute and subacute stages in rats.

Potential risk associated with new nanomaterial exposure needs to be assessed. This in vivo study investigated pulmonary effects of engineered cadmium-containing silica nanoparticles Cd/SiNPs (1 mg/rat), silica SiNPs (600 µg/rat) and CdCl2 (400 µg/rat) 1, 7 and 30 days after intratracheal instillation. Comprehensive histopathological and immunocytochemical characterization of lung damage in terms of apoptosis, cell proliferation, inflammation, fibrosis and metabolism were obtained. After exposure to all treatments, lung parenchyma showed injury patterns characterized by collapsed alveoli, inflammation, granuloma formation, thickened alveolar septa and bronchiolar epithelium exfoliation. Type II pneumocytes, containing scarcely surfactant-lamellated bodies, were also observed. Apoptotic phenomena enhanced as following, Cd/SiNPs>CdCl2> SiNPs. In parallel with these findings, a significant increase of PCNA-immunoreactive cells was detected together with high mitotic activity. Cellular localization and distribution of IL-6, IP-10 and TGF-ß1 revealed an increased expression of these cytokines as evidence of an enhanced cellular inflammatory response. CYP450-immunoreactivity was also enhanced, at bronchiolar (e.g. Clara cells) and alveolar (e.g. macrophages) level after both Cd/SiNPs and CdCl2. These overall effects were observed acutely and lasted until the 30th day, with Cd/SiNPs producing the most marked effects. Collagen-immunolabelling changed particularly 7 and 30 days after Cd/SiNPs, when a strong stromal fibrogenic reaction occurred. The present findings suggest that Cd/SiNPs produce significantly greater pulmonary alterations than either SiNPs or CdCl2 under the present experimental conditions.

Long-lasting oxidative pulmonary insult in rat after intratracheal instillation of silica nanoparticles doped with cadmium.

Silica/cadmium containing nanomaterials are now produced on industrial scale due to their potential for a variety of technological applications. Nevertheless, information on toxicity, exposure and health impact of these nanomaterials is still limited. In this study, in vivo effects of silica nanoparticles (SiNPs) doped with Cd (SiNPs-Cd, 1mg/rat), soluble CdCl(2) (400 µg/rat), or SiNPs (600 µg/rat) have been investigated by evaluating F(2)-isoprostanes (F(2)-IsoPs), superoxide dismutase (SOD1), inducible nitric oxide synthase (iNOS) and cyclooxygenase type 2 (COX-2) enzymes, as markers of oxidative stress, 24h, 7 and 30 days after intra-tracheal (i.t.) instillation to rats. Free and esterified F(2)-IsoPs were evaluated in lung and plasma samples by GC/NICI-MS/MS analysis, and SOD1, iNOS and COX-2 expression in pulmonary tissue by immunocytochemistry. Thirty days after exposure, pulmonary total F(2)-IsoPs were increased by 56% and 43% in CdCl(2) and SiNPs-Cd groups, respectively, compared to controls (32.8 ± 7.8 ng/g). Parallel elevation of free F(2)-IsoPs was observed in plasma samples (by 113% and 95% in CdCl(2) and SiNPs-Cd groups, respectively), compared to controls (28 ± 8 pg/ml). These effects were already detectable at day 7 and lasted until day 30 post-exposure. Pulmonary SOD1-, iNOS-, and COX-2-immunoreactivity was significantly enhanced in a time-dependent manner (7 days <30 days) after both CdCl(2) and SiNPs-Cd treatments. SiNPs did not influence any of the evaluated endpoints. The results indicate the capacity of engineered SiNPs-Cd to cause long-lasting oxidative tissue injury following pulmonary exposure in rat.

An insidious skin rash without itch.

A 74-year-old female with a 5-year medical history of breast infiltrating lobular carcinoma was admitted to our Rehabilitation Unit ward for left hemiparesis secondary to neurosurgical removal of frontal and right parietal metastatic lesions. After the intervention, prophylactic treatment with the antiepileptic diphenylhydantoin 100 mg/tid was started. On 38th day of drug administration an erythema without itch appeared in jugular and parasternal region and absent in the clothing covered areas, suggesting a contact dermatitis. Next day, the erythema extended to the neck with poorly delineated red plaques. During the following 4 days the patient presented oral stomatitis with fetid breath, atypical targetoid and erythematous confluenced macules. The clinical picture rapidly worsened with vesiculate, bullate lesions and frank skin erosions. The patient was sent to a Dermatology Burn Unit where a therapy with corticosteroids, antibiotics, fluids, albumin and immunoglobulins was administrated. Complete clinical resolution was observed after 1 month without long-term sequelae. Toxic epidermal necrolysis (TEN) is a rare (incidence about 0.01%) adverse drug reaction related to idiosyncratic mechanism, burdened by a mortality rate ranging from 3.2 to 90%. In our patient, TEN covered 63% of body surface, a condition associated with a death risk of 58.3% according to the specific severity illness scale SCORTEN. The disease onset may be insidious, and it could appear as a skin rash without itch; the cutaneous manifestations appear quite lately, then the disease quickly progresses. Early recognition of the disease, especially in oncologic patients, is critical for effective management of this condition in terms of mortality reduction.

Prolonged ethanol ingestion enhances benzene myelotoxicity and lowers urinary concentrations of benzene metabolite levels in CD-1 male mice.

Benzene toxicity is attributed to its metabolism, which is primarily mediated by the ethanol-inducible cytochrome P450 2E1 isoform (CYP2E1). The present study investigated the myelotoxicity and urinary concentrations of major benzene metabolites in adult CD-1 male mice treated with low levels of benzene vapors, ethanol, or a combination of the two. Groups of ethanol-treated (5% in a Lieber-DeCarli liquid diet, 3 weeks) or pair-fed control mice were exposed to 10 ppm benzene, 6 h per day, 5 days per week for 2 weeks, starting from the second week of ethanol administration. On the last day of treatment, the number of early and late erythroid progenitors (BFU-E and CFU-E) was reduced by 55%, while the number of granulocyte/macrophage progenitors (CFU-GM) was reduced by 36% in benzene-treated mice. Ethanol lowered the CFU-E, BFU-E, and CFU-GM colony formation by 33, 28, and 12%, respectively. In animals coexposed to benzene and ethanol, the CFU-E colony counts were decreased by 70%, the BFU-E by 80%, and the CFU-GM by 45%. Phenol (Ph), hydroquinone (HQ), catechol (Cat), and trans,trans-muconic acid (MA) were measured by HPLC-UV in urine samples collected weekly during the last 6-h benzene/air exposure session. In benzene-exposed mice urinary metabolite levels peaked at the end of the first week of treatment (microg/kg body weight (bw): Ph: 4931 +/- 1055; Cat: 109 +/- 17; HQ: 784 +/- 137; MA: 534 +/- 92) and significantly decreased at the end of the second week (microg/kg bw: Ph: 3909 +/- 984; Cat: 82 +/- 24; HQ: 337 +/- 72; MA: 235 +/- 55). In mice given benzene and ethanol, the urinary levels of Ph, Cat, HQ, and MA were significantly lower than those measured in the group given benzene alone. The urinary levels of Ph and Cat showed a decreasing trend, again, from the first to the second week of benzene exposure. These data indicate that chronic ethanol ingestion exacerbates benzene myelotoxicity and, in addition, reduces the urinary excretion of benzene metabolites in mice, suggesting that the influence of ethanol intake should be considered carefully in biomonitoring benzene exposure.

Platelet monoamine oxidase B activity as a state marker for alcoholism: trend over time during withdrawal and influence of smoking and gender.

AIMS AND METHODS: The present study evaluated time-related changes in platelet monoamine oxidase B (MAO-B) activity in an Italian cohort of alcohol-dependent subjects (n = 98) during early abstinence, and the effect of potential confounding factors, such as gender and smoking status, on the temporal trend of the enzyme activity. RESULTS: While still under the influence of ethanol (time point T1), the mean value of platelet MAO-B activity in alcoholics was 6.4 +/- 3.1 nmol/mg of protein/h. This increased by >40% (to 9.3 +/- 4.4 nmol/mg of protein/h) after 8 days of withdrawal (T2), and remained stable thereafter (T3 and T4: 15 and 22 days of abstinence, respectively). In a cohort of 138 healthy subjects, MAO activity levels averaged 9.9 +/- 0.9 nmol/mg of protein/h. In the group of alcoholic patients, alcohol intake cessation was confirmed by the progressive decrease of serum % carbohydrate-deficient transferrin (CDT), which was pathologically above the reference limits (6%) at T1 (7.8 +/- 3.3%), declined to 6.6 +/- 2.1% at T2 and reached physiological values at T3 and T4. In a subgroup of cirrhotic alcoholics, %CDT did not decrease over time, while MAO activity rose after the first week of abstinence, without further change at T3 and T4. During early withdrawal, neither gender nor tobacco smoking affected the temporal pattern of MAO activity. CONCLUSIONS: MAO-B can be regarded as a state marker of alcohol consumption. The temporal pattern of platelet MAO-B activity may be used for the diagnostic assessment of alcoholism and early abstinence, regardless of gender and smoking status.