The impact of a newly established specialized pediatric epilepsy center in Tanzania: An observational study

Purpose: This study evaluated the impact of a newly established clinic for the diagnosis of pediatric epilepsy in a resource-limited center (Ifakara, Tanzania). Methods: Patients aged 0-18 years referred to the Pediatric Epilepsy Unit of Saint Francis Referral Hospital were recruited. Demographic and clinical data were collected through Kobo Toolbox and analyzed through a descriptive analysis.. Results: 143 patients were evaluated, and for 48 of them an EEG was recorded (abnormalities were detected in 80.85% of the cases). The diagnosis of epilepsy was confirmed in 87 patients. Focal epilepsy was diagnosed in 57 patients, generalized epilepsy in 24 patients, and forms of unknown onset in 6 patients. Epilepsy was excluded for 9 children. Etiologies included hypoxic-ischemic encephalopathy (39%), central nervous system infections (3.4%), and genetic diseases (3.4%). A specific epilepsy syndrome was diagnosed in 16 patients. 74 patients were under treatment; the most used antiseizure medication (ASM) was phenobarbital (43.36%), followed by carbamazepine (16.08%), sodium valproate (11.19%), phenytoin (2.8%), and lamotrigine (0.7%). Therapeutic changes were proposed to 95 patients, more frequently consisting of withdrawing phenobarbital (39.16%), switching to sodium valproate (27.97%), switching to or adjusting carbamazepine dosage (27.27%), and starting prednisone (2.8%). 76% of the patients with confirmed epilepsy achieved complete seizure freedom at the fourth follow-up consultation. Conclusions: Our data depicted the epilepsy spectrum and highlighted the prognostic implications of improving the availability of ASMs such as sodium valproate and second- and third-generation ones in resource-limited countries

Cardio-facio-cutaneous syndrome and gastrointestinal defects: report on a newborn with 19p13.3 deletion including the MAP 2K2 gene

Background: Cardio-facio-cutaneous syndrome (CFCS) belongs to RASopathies, a group of conditions caused by mutations in genes encoding proteins of the rat sarcoma/mitogen-activated protein kinase (RAS/MAPK) pathway. It is a rare syndrome, with about 300 patients reported. Main clinical manifestations include facial dysmorphisms, growth failure, heart defects, developmental delay, and ectodermal abnormalities. Mutations (mainly missense) of four genes (BRAF, MAP 2 K1, MAP 2 K2, and KRAS) have been associated to CFCS. However, whole gene deletions/duplications and chromosomal microdeletions have been also reported. Specifcally, 19p13.3 deletion including MAP 2 K2 gene are responsible for cardio-facio-cutaneous microdeletion syndrome, whose afected subjects show more severe phenotype than CFCS general population. Case presentation: Hereby, we report on a female newborn with prenatal diagnosis of omphalocele, leading to further genetic investigations through amniocentesis. Among these, array comparative genomic hybridization (a-CGH) identifed a 19p13.3 microdeletion, spanning 1.27Mb and including MAP 2 K2 gene. Clinical features at birth (coarse face with dysmorphic features, sparse and friable hair, cutaneous vascular malformations and hyperkeratotic lesions, interventricular septal defect, and omphalocele) were compatible with CFCS diagnosis, and further postnatal genetic investigations were not considered necessary. Soon after discharge, at around 1month of life, she was readmitted to our Neonatal Intensive Care Unit due to repeated episodes of vomiting, subtending a hypertrophic pyloric stenosis (HPS) which was promptly identifed and treated. Conclusions: Our report supports the 19p13.3 microdeletion as a contiguous gene syndrome, in which the involvement of the genes contiguous to MAP 2 K2 may modify the patients’ phenotype. It highlights how CFCS afected subjects, including those with 19p13.3 deletions, may have associated gastrointestinal defects (e.g., omphalocele and HPS), providing further data on 19p13.3 microdeletion syndrome, and a better characterization of its genomic and phenotypic features. The complex clinical picture of such patients may be worsened by additional, and even precocious, life-threatening conditions like HPS. Clinicians must consider, anticipate and/or promptly treat possible medical and surgical complications, with the aim of reducing adverse outcomes. Extensive diagnostic work-up, and early, continuous, and multidisciplinary follow-up, as well as integrated care, are necessary for the longitudinal clinical evolution of any single patient

Zinc protection in cadmium-induced Blood Brain Barrier permeability: a metabolic and morphological in vitro study

Cadmium (Cd) is a worldwide occupational and environmental pollutant [1]. Cd toxicity is widely known and studied in many tissues and organs such as testis, kidney, liver, lung and brain [2,3]. On the other hand, zinc (Zn) is a trace element known as coenzyme for many proteins such as methallothionein [4]. To date, very little is known about the role of Cd and Zn in BBB permeability. To study their effects in BBB permeability in vitro, the RBE4 cell line was used and different concentrations of CdCl2 and ZnCl2 were tested. Metabolic activity (MTT assay) was performed to test the protective and preventive role of ZnCl2 on CdCl2 toxicity. Western blotting analysis was used to better investigate the molecular pathway involved in Cd-induced BBB permeability evaluating GRP78 (ER stress marker) and caspase-3 protein expression levels. Furthermore, ZO-1 and F-actin immunofluorescent staining was performed to better understand the morphological alterations and BBB permeability achieved by Cd treatment. Our preliminary data highlight the role of Cd in evoking BBB permeability by F-actin and ZO1 dislocations, triggering the caspase-3 molecular pathway activation induced by GRP78-ER stress increase. Moreover, the data clearly show how Zn is able to counteract the metabolic impairment induced by Cd treatment. Taken together these data point out the possible role of Zn in counteracting the Cd-induced BBB impairment

The Relationship between Working Night Shifts and Depression among Nurses : A Systematic Review and Meta-Analysis

Background: For many years, occupational physicians have debated whether there is a link between working the night shift and depression and other co-occurring mental health issues, with an emphasis on work-related, biological, individual, and environmental factors. We performed this systematic review and meta-analysis to estimate the overall association between sleep deprivation and depression among nurses working night shifts. Methods: A systematic search as carried out across the electronic databases PubMed, Scopus, and Web of Science from inception to 30 September 2022, for studies that reported a relationship between estimated night shift work and depression in nurses. The outcomes were measured using the odds ratio (OR) and matching 95% confidence interval (CI). The I2 statistic was used to assess heterogeneity. The Grading of Recommendations Assessment, Development and Evaluation technique was used to evaluate the quality of the evidence, and the Newcastle–Ottawa Scale was utilized to assess the methodological quality of each of the included studies. We determined the overall relationship between working nights and the onset of depression. Results: A total of 20 studies were included in the systematic review. Furthermore, 8 studies were included in the meta-analysis due to their common use of the OR as an effect measure. The 8 studies gave an overall estimate indicating a statistically significant association between night shift work and depression among nurses (OR = 1.49 95% CI: 1.26, 1.76). The prediction interval for the overall estimate was (0.995, 2.231). This implies that the true OR in a future study would most likely fall within this range, with a 95% certainty. Conclusions: The outcome of this systematic review and meta-analysis showed a significant association between night shift work, the circadian and sleep disruption it causes, and the risk of depression in nurses. This demonstrates that nurses who work night shifts are at risk of developing depression.publishedVersionPeer reviewe

HER2 isoforms co-expression differently tunes mammary tumor phenotypes affecting onset, vasculature and therapeutic response

Full-length HER2 oncoprotein and splice variant Delta16 are co-expressed in human breast cancer. We studied their interaction in hybrid transgenic mice bearing human full-length HER2 and Delta16 (F1 HER2/Delta16) in comparison to parental HER2 and Delta16 transgenic mice. Mammary carcinomas onset was faster in F1 HER2/Delta16 and Delta16 than in HER2 mice, however tumor growth was slower, and metastatic spread was comparable in all transgenic mice. Full-length HER2 tumors contained few large vessels or vascular lacunae, whereas Delta16 tumors presented a more regular vascularization with numerous endothelium-lined small vessels. Delta16-expressing tumors showed a higher accumulation of i.v. injected doxorubicin than tumors expressing full-length HER2. F1 HER2/Delta16 tumors with high full-length HER2 expression made few large vessels, whereas tumors with low full-length HER2 and high Delta16 contained numerous small vessels and expressed higher levels of VEGF and VEGFR2. Trastuzumab strongly inhibited tumor onset in F1 HER2/Delta16 and Delta16 mice, but not in full-length HER2 mice. Addiction of F1 tumors to Delta16 was also shown by long-term stability of Delta16 levels during serial transplants, in contrast full-length HER2 levels underwent wide fluctuations. In conclusion, full-length HER2 leads to a faster tumor growth and to an irregular vascularization, whereas Delta16 leads to a faster tumor onset, with more regular vessels, which in turn could better transport cytotoxic drugs within the tumor, and to a higher sensitivity to targeted therapeutic agents. F1 HER2/Delta16 mice are a new immunocompetent mouse model, complementary to patient-derived xenografts, for studies of mammary carcinoma onset, prevention and therapy

Early stability and late random tumor progression of a HER2-positive primary breast cancer patient-derived xenograft

We established patient-derived xenografts (PDX) from human primary breast cancers and studied whether stability or progressive events occurred during long-term in vivo passages (up to 4 years) in severely immunodeficient mice. While most PDX showed stable biomarker expression and growth phenotype, a HER2-positive PDX (PDX-BRB4) originated a subline (out of 6 studied in parallel) that progressively acquired a significantly increased tumor growth rate, resistance to cell senescence of in vitro cultures, increased stem cell marker expression and high lung metastatic ability, along with a strong decrease of BCL2 expression. RNAseq analysis of the progressed subline showed that BCL2 was connected to three main hub genes also down-regulated (CDKN2A, STAT5A and WT1). Gene expression of progressed subline suggested a partial epithelial-to-mesenchymal transition. PDX-BRB4 with its progressed subline is a preclinical model mirroring the clinical paradox of high level-BCL2 as a good prognostic factor in breast cancer. Sequential in vivo passages of PDX-BRB4 chronically treated with trastuzumab developed progressive loss of sensitivity to trastuzumab while HER2 expression and sensitivity to the pan-HER tyrosine kinase inhibitor neratinib were maintained. Long-term PDX studies, even though demanding, can originate new preclinical models, suitable to investigate the mechanisms of breast cancer progression and new therapeutic approaches

Segmental transverse colectomy. Minimally invasive versus open approach: results from a multicenter collaborative study

none65noThe role of minimally invasive surgery in the treatment of transverse colon cancer is still controversial. The aim of this study is to investigate the advantages of a totally laparoscopic technique comparing open versus laparoscopic/robotic approach. Three hundred and eighty-eight patients with transverse colon cancer, treated with a segmental colon resection, were retrospectively analyzed. Demographic data, tumor stage, operative time, intraoperative complications, number of harvested lymph nodes and recovery outcomes were recorded. Recurrences and death were also evaluated during the follow-up. No differences were found between conventional and minimally invasive surgery, both for oncological long-term outcomes (recurrence rate p = 0.28; mortality p = 0.62) and postoperative complications (overall rate p = 0.43; anemia p = 0.78; nausea p = 0.68; infections p = 0.91; bleeding p = 0.62; anastomotic leak p = 0.55; ileus p = 0.75). Nevertheless, recovery outcomes showed statistically significant differences in favor of minimally invasive surgery in terms of time to first flatus (p = 0.001), tolerance to solid diet (p = 0.017), time to first mobilization (p = 0.001) and hospital stay (p = 0.004). Compared with laparoscopic approach, robotic surgery showed significantly better results for time to first flatus (p = 0.001), to first mobilization (p = 0.005) and tolerance to solid diet (p = 0.001). Finally, anastomosis evaluation confirmed the superiority of intracorporeal approach which showed significantly better results for time to first flatus (p = 0.001), to first mobilization (p = 0.003) and tolerance to solid diet (p = 0.001); moreover, we recorded a statistical difference in favor of intracorporeal approach for infection rate (p = 0.04), bleeding (p = 0.001) and anastomotic leak (p = 0.03). Minimally invasive approach is safe and effective as the conventional open surgery, with comparable oncological results but not negligible advantages in terms of recovery outcomes. Moreover, we demonstrated that robotic approach may be considered a valid option and an intracorporeal anastomosis should always be preferred.noneMilone, Marco; Degiuli, Maurizio; Velotti, Nunzio; Manigrasso, Michele; Vertaldi, Sara; D'Ugo, Domenico; De Palma, Giovanni Domenico; Dario Bruzzese, Giuseppe Servillo, Giuseppe De Simone, Katia Di Lauro, Silvia Sofia, Marco Ettore Allaix, Mario Morino, Rossella Reddavid, Carlo Alberto Ammirati, Stefano Scabini, Gabriele Anania, Cristina Bombardini, Andrea Barberis, Roberta Longhin, Andrea Belli, Francesco Bianco, Giampaolo Formisano, Giuseppe Giuliani, Paolo Pietro Bianchi, Davide Cavaliere, Leonardo Solaini, Claudio Coco, Gianluca Rizzo, Andrea Coratti, Raffaele De Luca, Michele Simone, Alberto Di Leo, Giovanni De Manzoni, Paola De Nardi, Ugo Elmore, Riccardo Rosati, Andrea Vignali, Paolo Delrio, Ugo Pace, Daniela Rega, Antonio Di Cataldo, Giovanni Li Destri, Annibale Donini, Luigina Graziosi, Andrea Fontana, Michela Mineccia, Sergio Gentilli, Manuela Monni, Mario Guerrieri, Monica Ortenzi, Francesca Pecchini, Micaela Piccoli, Italy. Corrado Pedrazzani, Giulia Turri, Sara Pollesel, Franco Roviello, Marco Rigamonti, Michele Zuolo, Mauro Santarelli, Federica Saraceno, Pierpaolo Sileri Giuseppe Sigismondo Sica, Luigi Siragusa Salvatore Pucciarelli, Matteo ZuinMilone, Marco; Degiuli, Maurizio; Velotti, Nunzio; Manigrasso, Michele; Vertaldi, Sara; D'Ugo, Domenico; De Palma, Giovanni Domenico; Dario Bruzzese, Giuseppe Servillo, Giuseppe De Simone, Katia Di Lauro, Silvia Sofia, Marco Ettore Allaix, Mario Morino, Rossella Reddavid, Carlo Alberto Ammirati, Stefano Scabini, Gabriele Anania, Cristina Bombardini, Andrea Barberis, Roberta Longhin, Andrea Belli, Francesco Bianco, Giampaolo Formisano, Giuseppe Giuliani, Paolo Pietro Bianchi, Davide Cavaliere, Leonardo Solaini, Claudio Coco, Gianluca Rizzo, Andrea Coratti, Raffaele De Luca, Michele Simone, Alberto Di Leo, Giovanni De Manzoni, Paola De Nardi, Ugo Elmore, Riccardo Rosati, Andrea Vignali, Paolo Delrio, Ugo Pace, Daniela Rega, Antonio Di Cataldo, Giovanni Li Destri, Annibale Donini, Luigina Graziosi, Andrea Fontana, Michela Mineccia, Sergio Gentilli, Manuela Monni, Mario Guerrieri, Monica Ortenzi, Francesca Pecchini, Micaela Piccoli, Italy. Corrado Pedrazzani, Giulia Turri, Sara Pollesel, Franco Roviello, Marco Rigamonti, Michele Zuolo, Mauro Santarelli, Federica Saraceno, Pierpaolo Sileri Giuseppe Sigismondo Sica, Luigi Siragusa Salvatore Pucciarelli, Matteo Zui