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Abstract TBX4 gene, located on human chromosome 17q23.2, encodes for T-Box Transcription Factor 4, a transcription factor that belongs to the T-box gene family and it is involved in the regulation of some embryonic developmental processes, with a significant impact on respiratory and skeletal illnesses. Herein, we present the case of a female neonate with persistent pulmonary hypertension (PH) who underwent extracorporeal membrane oxygenation (ECMO) on the first day of life and then resulted to have a novel variant of the TBX4 gene identified by Next-Generation Sequencing. We review the available literature about the association between PH with neonatal onset or emerging during the first months of life and mutations of the TBX4 gene, and compare our case to previously reported cases. Of 24 cases described from 2010 to 2023 sixteen (66.7%) presented with PH soon after birth. Skeletal abnormalities have been described in 5 cases (20%). Eleven cases (46%) were due to de novo mutations. Three patients (12%) required ECMO. Identification of this variant in affected individuals has implications for perinatal and postnatal management and genetic counselling. We suggest including TBX4 in genetic studies of neonates with pulmonary hypertension, even in the absence of skeletal abnormalities.

Intracranial hemorrhage may represent a complication of the perinatal period that affects neonatal morbidity and mortality. Very poor data exist about a possible association between mutations of the type IV collagen a1 chain (COL4A1) gene and the development of intracranial hemorrhage, and only sporadic reports focus on intracerebral bleedings already developing in utero or in the neonatal period in infants with such a mutation. This study presents a case series of term neonates affected by intracranial hemorrhage, with no apparent risk factors for the development of this condition, who were carriers of COL4A1 gene variants. This study also provides a review of the most recent scientific literature on this topic, specifically focusing on the available scientific data dealing with the perinatal period.

The production of beer, a beverage of global cultural and industrial importance, has a significant impact on the environment due to the use of natural resources and the emissions generated during the various stages of the production process. Therefore, this article examines the sustainability of beer production through a review of literature articles that have used Life Cycle Assessment (LCA) to assess its environmental impacts. A systematic literature review was conducted by selecting peer-reviewed articles published between 2001 and July 2024 using databases such as Scopus and Google Scholar. The search included studies analyzing different stages of the beer life cycle, from raw material production to packaging and distribution, using specific keywords related to LCA and brewing. The results showed that energy use and packaging are the two critical aspects identified in the review, which represent a significant part of the environmental footprint. However, it is important to note that the available studies on the subject are few and heterogeneous and they use different methodologies, impact categories, and functional units, which complicates the comparison and synthesis of results, limiting the ability to draw definitive conclusions. Recommendations were made to improve sustainability, including the adoption of more efficient technologies, the use of recycled materials for packaging, and the implementation of sustainable agricultural practices. These strategies could aim to significantly reduce the overall environmental impact of beer production.

IntroductionAssessing the treatment response of glioblastoma multiforme during immunotherapy (IT) is an open issue. Treatment response assessment maps (TRAMs) might help distinguish true tumor progression (TTP) and pseudoprogression (PsP) in this setting.MethodsWe recruited 16 naïve glioblastoma patients enrolled in a phase II trial consisting of the Stupp protocol (a standardized treatment for glioblastoma involving combined radiotherapy and chemotherapy with temozolomide, followed by adjuvant temozolomide) plus IT with dendritic cells. Patients were followed up till progression or death; seven underwent a second surgery for suspected progression. Clinical, immunological, and MRI data were collected from all patients and histology in case of second surgery. Patients were classified as responders (progression-free survival, PFS > 12 months), and non-responders (PFS ≤ 12), HIGH-NK (natural killer cells, i.e., immunological responders), and LOW-NK (immunological non-responders) based on immune cell counts in peripheral blood. TRAMs differentiate contrast-enhancing lesions with different washout dynamics into hypothesized tumoral (conventionally blue-colored) vs. treatment-related (red-colored).ResultsUsing receiver operating characteristic (ROC) curves, a threshold of −0.066 in VBlue/VCE (volume of the blue portion of tumoral area/volume of contrast enhancement) variation between values obtained in the MRI performed before PsP/TTP and at TTP/PSP allowed to discriminate TTP from PsP with a sensitivity of 71.4% and a specificity of 100%. Among HIGH-NK patients, at month 6 there was a significant reduction compared to baseline and month 2 in median “blue” volumes.DiscussionIn conclusion, in our pilot study TRAMs support the discrimination between tumoral and treatment-related enhancing features in immunological responders vs. non-responders, the distinction between PsP and TTP, and might provide surrogate markers of immunological response.

Summary: Background: Despite the overall improvement in care, people with type 2 diabetes (T2D) experience an excess risk of end-stage kidney disease. We evaluated the long-term effectiveness of dapagliflozin on kidney function and albuminuria in patients with T2D. Methods: We included patients with T2D who initiated dapagliflozin or comparators from 2015 to 2020. Propensity score matching (PSM) was performed to balance the two groups. The primary endpoint was the change in estimated glomerular filtration rate (eGFR) from baseline to the end of observation. Secondary endpoints included changes in albuminuria and loss of kidney function. Findings: We analysed two matched groups of 6197 patients each. The comparator group included DPP-4 inhibitors (40%), GLP-1RA (22.3%), sulphonylureas (16.1%), pioglitazone (8%), metformin (5.8%), or acarbose (4%). Only 6.4% had baseline eGFR 30 mg/g. During a mean follow-up of 2.5 year, eGFR declined significantly less in the dapagliflozin vs comparator group by 1.81 ml/min/1.73 m2 (95% C.I. from 1.13 to 2.48; p

Abstract Sjögren’s Syndrome (SjS) results in loss of salivary and lacrimal gland excretion due to an autoimmune attack on these secretory glands. Conventional SjS treatments address the symptoms, but not the cause of disease. Recognizing this deficit of treatments to reverse SjS disease, studies were pursued using the fimbriae from enterotoxigenic E. coli, colonization factor antigen I (CFA/I), which has anti-inflammatory properties. To determine if CFA/I fimbriae could attenuate SjS-like disease in C57BL/6.NOD-Aec1Aec2 (SjS) females, the Lactococcus lactis (LL) 301 strain was developed to chromosomally express the cfaI operon. Western blot analysis confirmed CFA/I protein expression, and this was tested in SjS females at different stages of disease. Repeated dosing with LL 301 proved effective in mitigating salivary flow loss and in reducing anti-nuclear antibodies (ANA) and inflammation in the submandibular glands (SMGs) in SjS females and in restoring salivary flow in diseased mice. LL 301 treatment reduced proinflammatory cytokine production with concomitant increases in TGF-β+ CD25+ CD4+ T cells. Moreover, LL 301 treatment reduced draining lymph and SMG follicular T helper (Tfh) cell levels and proinflammatory cytokines, IFN-γ, IL-6, IL-17, and IL-21. Such evidence points to the therapeutic capacity of CFA/I protein to suppress SjS disease and to have restorative properties in combating autoimmune disease.

In recent decades, increases in temperature and tropical rainfall have facilitated the spread of mosquito species into temperate zones. Mosquitoes are vectors for many viruses, including West Nile virus (WNV) and dengue virus (DENV), and pose a serious threat to public health. This review covers most of the current knowledge on the mosquito species associated with the transmission of WNV and DENV and their geographical distribution and discusses the main vertebrate hosts involved in the cycles of WNV or DENV. It also describes virological and pathogenic aspects of WNV or DENV infection, including emerging concepts linking WNV and DENV to the reproductive system. Furthermore, it provides an epidemiological analysis of the human cases of WNV and DENV reported in Europe, from 1 January 2018 to 31 December 2023, with a particular focus on Italy. The first autochthonous cases of DENV infection, with the most likely vector being Aedes albopictus, have been observed in several European countries in recent years, with a high incidence in Italy in 2023. The lack of treatments and effective vaccines is a serious challenge. Currently, the primary strategy to prevent the spread of WNV and DENV infections in humans remains to limit the spread of mosquitoes.

Physiology and behavior are structured temporally to anticipate daily cycles of light and dark, ensuring fitness and survival. Neuromodulatory systems in the brain—including those involving serotonin and dopamine—exhibit daily oscillations in neural activity and help shape circadian rhythms. Disrupted neuromodulation can cause circadian abnormalities that are thought to underlie several neuropsychiatric disorders, including bipolar mania and schizophrenia, for which a mechanistic understanding is still lacking. Here, we show that genetically depleting serotonin in Tph2 knockout mice promotes manic-like behaviors and disrupts daily oscillations of the dopamine biosynthetic enzyme tyrosine hydroxylase (TH) in midbrain dopaminergic nuclei. Specifically, while TH mRNA and protein levels in the Substantia Nigra (SN) and Ventral Tegmental Area (VTA) of wild-type mice doubled between the light and dark phase, TH levels were high throughout the day in Tph2 knockout mice, suggesting a hyperdopaminergic state. Analysis of TH expression in striatal terminal fields also showed blunted rhythms. Additionally, we found low abundance and blunted rhythmicity of the neuropeptide cholecystokinin (Cck) in the VTA of knockout mice, a neuropeptide whose downregulation has been implicated in manic-like states in both rodents and humans. Altogether, our results point to a previously unappreciated serotonergic control of circadian dopamine signaling and propose serotonergic dysfunction as an upstream mechanism underlying dopaminergic deregulation and ultimately maladaptive behaviors.

BackgroundThe lung ultrasound (LUS) score can be a useful tool to predict the need for respiratory support and the length of hospital stay in infants with bronchiolitis.ObjectiveTo compare lung ultrasound features in neonates and infants up to three months of age with bronchiolitis to determine whether LUS scores (range 0–36) differ in infants with coinfections or not.MethodsNeonates and infants younger than three months admitted to neonatal units from October 2022 to March 2023, who underwent lung ultrasound evaluation on admission, were included in this retrospective study.ResultsWe included 60 patients who underwent LUS evaluation at admission. Forty-two infants (70.0%) had a single viral infection. Eighteen infants (30.0%) had a coinfection: fifteen infants (25.0%) had more than one virus at PCR; one infant (1.7%) had both a viral coinfection and a viral-bacteria coinfection; two infants (3.3%) had viral-bacteria coinfection. Infants with a single viral infection and those with coinfections had similar LUS scores globally and in different lung zones. An LUS score higher than 8 was identified to significantly predict the need for any respiratory support (p = 0.0035), whereas an LUS score higher than 13 was identified to significantly predict the need for mechanical ventilation (p = 0.024).ConclusionIn our small cohort of neonates and infants younger than three months hospitalized with bronchiolitis, we found no statistically significant differences in the LUS score on admission between patients with a single viral infection and those with multiple infections.

Moment-resisting frames (MRFs) and eccentrically braced frames (EBFs) can be effectively combined in multi-story steel buildings. In fact, MRFs provide redundancy and ductility, while EBFs provide initial and post-yield stiffness with high energy dissipation capacity. In addition, if detachable links are designed as dissipative fuses, it is possible to activate their almost contemporary yielding and prevent the collapse of structures during severe earthquakes, ensuring easy repair and rehabilitation measures. The seismic responses of dual frames with MRFs and EBFs are investigated by means of pushover analyses. Different buildings were designed, varying the number of floors (two, four, and eight stories), the number of MRF spans (zero, one, and two), and the length of the short links (0.8 Mp/Vp and 1.6 Mp/Vp). The obtained results confirmed the superior behavior of dual frames with respect to simple EBFs. In addition, it was observed that the frames with the shorter links exhibited higher resistance and rigidity but smaller overall displacement capacity because of the anticipated failure of the links.

Given the various clinical manifestations that characterize Coronavirus Disease 2019 (COVID-19), the scientific community is constantly searching for biomarkers with prognostic value. Surfactant proteins A (SP-A) and D (SP-D) are collectins that play a crucial role in ensuring proper alveolar function and an alteration of their serum levels was reported in several pulmonary diseases characterized by Acute Respiratory Distress Syndrome (ARDS) and pulmonary fibrosis. Considering that such clinical manifestations can also occur during Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, we wondered if these collectins could act as prognostic markers. In this regard, serum levels of SP-A and SP-D were measured by enzyme immunoassay in patients with SARS-CoV-2 infection (n = 51) at admission (T0) and after seven days (T1) and compared with healthy donors (n = 11). SP-D increased in COVID-19 patients compared to healthy controls during the early phases of infection, while a significant reduction was observed at T1. Stratifying SARS-CoV-2 patients according to disease severity, increased serum SP-D levels were observed in severe compared to mild patients. In light of these results, SP-D, but not SP-A, seems to be an eligible marker of COVID-19 pneumonia, and the early detection of SP-D serum levels could be crucial for preventive clinical management.