A Gain-of-Function Mutation on Gene and Its Possible Pathogenic Role in Branched-Chain Amino Acid Metabolism.

BCKDK is an important key regulator of branched-chain ketoacid dehydrogenase complex activity by phosphorylating and so inactivating branched-chain ketoacid dehydrogenases, the rate-limiting enzyme of the branched-chain amino acid metabolism. We identified, by whole exome-sequencing analysis, the p.His162Gln variant of the gene in a neonate, picked up by newborn screening, with a biochemical phenotype of a mild form of maple syrup urine disease (MSUD).

Modelling the COVID-19 Pandemic Effects on Employees' Health and Performance: A PLS-SEM Mediation Approach.

The COVID-19 pandemic has resulted in the imposition of certain changes in the management of organizations and in the behavior and actions of employees. The purpose of this paper is to investigate the impact of COVID-19 pandemic effects on employees' health and mental well-being, as well as on their working performance. Moreover, the paper aims to highlight whether health- and work-related stress factors mediate the above relations.

Newborn Screening for Biotinidase Deficiency. The Experience of a Regional Center in Italy.

Biotinidase deficiency (BD) is an autosomal recessive disease causing a defect in the biotin-releasing enzyme. Newborn screening (NBS) allows early diagnosis and treatment, ensuring excellent prognosis. The aim of this study was to describe our experience in the diagnosis, treatment, and follow-up showing key strategies and unsolved questions of the management of BD patients.

Diagnosis, genetic characterization and clinical follow up of mitochondrial fatty acid oxidation disorders in the new era of expanded newborn screening: A single centre experience.

Introduction: Mitochondrial fatty acid oxidation disorders (FAODs) are a heterogeneous group of hereditary autosomal recessive diseases included in newborn screening (NBS) program in Italy. The aim of this study was to analyse FAODs cases, identified either clinically or by NBS,for clinical and genetic characterization and to evaluate a five years' experience of NBS, in the attempt to figure out the complexity of genotype-phenotype correlation and to confirm the clinical impact of NBS in our centre experience.

Materials And Methods: We analysed FAODs patients diagnosed either by NBS or clinically, followed since February 2014 to April 2019 at the Regional Screening Centre and Inherited Metabolic Diseases Unit of Verona.

Modeling the Pathways of Knowledge Management Towards Social and Economic Outcomes of Health Organizations.

Despite the increasing emphasis placed on knowledge management (KM) by the business sector and the common belief that creating, acquiring, sharing, and the use of knowledge enable individuals, teams, and communities to achieve superior performance, within the healthcare context, there is still room from improvements from both the theoretical and empirical perspectives. The purpose of this paper is to outline the contribution of KM process to the social- and economic-related outcomes in the context of health organizations. Given the theoretical approach on the considered concepts and their relationships, a conceptual model and seven research hypotheses were proposed.

Induction of endoplasmic reticulum stress by aminosteroid derivative RM-581 leads to tumor regression in PANC-1 xenograft model.

The high fatality and morbidity of pancreatic cancer have remained almost unchanged over the last decades and new clinical therapeutic tools are urgently needed. We determined the cytotoxic activity of aminosteroid derivatives RM-133 (androstane) and RM-581 (estrane) in three human pancreatic cancer cell lines (BxPC3, Hs766T and PANC-1). In PANC-1, a similar level of antiproliferative activity was observed for RM-581 and RM-133 (IC = 3.

Altered expression of different GalNAc‑transferases is associated with disease progression and poor prognosis in women with high-grade serous ovarian cancer.

Protein glycosylation perturbations are implicated in a variety of diseases, including cancer. Aberrant glycosylation in cancer is frequently attributed to altered expression of polypeptide GalNAc transferases (GalNAc‑Ts) - enzymes initiating mucin-type O-glycosylation. A previous study from our group demonstrated that one member of this family (GALNT3) is overexpressed in epithelial ovarian cancer (EOC), and GALNT3 expression correlated with shorter progression-free survival (PFS) in EOC patients with advanced disease.

High-protein goat's milk diet identified through newborn screening: clinical warning of a potentially dangerous dietetic practice.

Objective: Breast-feeding is an unequalled way of providing optimal food for infants' healthy growth and development and the WHO recommends that infants should be exclusively breast-fed for the first 6 months of life. For mothers who are unable to breast-feed or who decide not to, infant formulas are the safest alternative. Despite recommendations, it is possible that parents make potentially harmful nutritional choices for their children because of cultural beliefs or misinformation on infant nutrition.

Vitamin B Administration by Subcutaneous Catheter Device in a Cobalamin A (cblA) Patient.

Cobalamin A deficiency (cblA) is an inherited disorder of intracellular cobalamin metabolism, caused by impaired 5'-deoxy-adenosylcobalamin (AdoCbl) synthesis. Hydroxocobalamin (OHCbl) is the cornerstone of cblA treatment because vitamin B12 may completely restore AdoCbl deficiency. Parenteral administration, intravenous, subcutaneous or intramuscular, is generally required to achieve effect.

Divergent Expression and Metabolic Functions of Human Glucuronosyltransferases through Alternative Splicing.

Maintenance of cellular homeostasis and xenobiotic detoxification is mediated by 19 human UDP-glucuronosyltransferase enzymes (UGTs) encoded by ten genes that comprise the glucuronidation pathway. Deep RNA sequencing of major metabolic organs exposes a substantial expansion of the UGT transcriptome by alternative splicing, with variants representing 20% to 60% of canonical transcript expression. Nearly a fifth of expressed variants comprise in-frame sequences that may create distinct structural and functional features.

Validation of EP1 Antibody Clone for Estrogen Receptor Immunohistochemistry for Breast Cancer.

Background: SP1 Rabbit monoclonal antibody to estrogen receptor (ER) has long been the standard for determination of ER status in breast cancer but has been replaced by the rabbit EP1 clone.

Aim: To validate the EP1 antibody clone for use in determination of breast cancer ER status in a large clinical population against the previous standard SP1.

Materials And Methods: ER immunohistochemistry was assessed in 523 consecutive cases from a clinical setting using tissue microarrays.

Analysis of the d3-growth hormone receptor polymorphism in large cohorts of small, appropriate and large for gestational age newborns.

Background: Several studies evidenced a possible role of the d3-Growth Hormone Receptor (GHR) polymorphism in fetal growth. The GHR genotype distribution was studied in small (SGA) and appropriate (AGA) for gestational age newborns but never in the large (LGA) for gestational age babies. The aim of this study was to evaluate the frequencies of this polymorphism in a large cohort of SGA, AGA and LGA newborns.

Pathologic response and long-term follow-up in breast cancer patients treated with neoadjuvant chemotherapy: a comparison between classifications and their practical application.

Context: Breast cancer is increasingly treated with neoadjuvant chemotherapy to improve surgical resectability and evaluate tumor response, which is assessed histopathologically. Several histopathologic classification systems have been previously described for assessment of treatment response.

Objectives: To test performance in a side-by-side comparison of several histopathologic classification systems after neoadjuvant chemotherapy with clinical outcome.

Value of sentinel node mapping in cancer of the cervix.

Objectives: To compare the relative value of two methods of detection for the sentinel lymphatic nodes (SLNs): colorimetric with Isosulfan blue (ISB) and radio-isotopic with Technetium-99 (Tc99), and to evaluate the concept of the SLN mapping applied to cervical cancer.

Methods: From October 2000 to December 2006, radical surgery was planned in 211 patients who presented early-stage cancer of the cervix. Both ISB and Tc99 were used to detect the SLNs.

Immunohistochemical expression of conjugating UGT1A-derived isoforms in normal and tumoral drug-metabolizing tissues in humans.

Glucuronidation by UDP-glucuronyltransferase (UGT) enzymes is the prevailing conjugative pathway for the metabolism of both xenobiotics and endogenous compounds. Alterations in this pathway, such as those generated by common genetic polymorphisms, have been shown to significantly impact on the health of individuals, influencing cancer susceptibility, responsiveness to drugs and drug-induced toxicity. Alternative usage of terminal exons leads to UGT1A-derived splice variants, namely the classical and enzymatically active isoforms 1 (i1) and the novel enzymatically inactive isoforms 2 (i2).

Immunohistochemical analysis of possible chemoresistance markers identified by micro-arrays on serous ovarian carcinomas.

Using the DNA microarray technology, we have identified genes that are differentially expressed in chemosensitive and chemoresistant ovarian serous papillary carcinomas and could potentially distinguish ovarian cancer patients based on their response to chemotherapy. The present study aims to evaluate the clinical usefulness of overexpression of selected genes by immunohistochemistry. Our cohort included 158 women who were operated on and received chemotherapy for an advanced serous papillary ovarian carcinoma (FIGO stages III and IV).

Identification of PCA3 (DD3) in prostatic carcinoma by in situ hybridization.

PCA3 is a specific marker of prostatic carcinoma. However, PCA3 has been detected only at RNA level and a corresponding PCA3 protein has never been identified. The aim of this study was to develop a technique capable of detecting PCA3 RNA on histology sections and to assess the cellular location of the molecule.

SHP-1 tyrosine phosphatase in human erythrocytes.

SHP-1 is a SH2-domain containing protein Tyr-phosphatase expressed in hematopoietic cell lines, which is hypothesized to play a negative role in signal transduction. In human erythrocytes, the phospho-Tyr level of proteins, mainly transmembrane band 3, is closely controlled by the antithetic activity of Tyr-protein kinases and phosphatases, resulting in a dephosphorylated state. Only after particular stimuli, as with oxidizing agents, diamide or pervanadate, or thiol alkylating compound, N-ethyl maleimide (NEM), Tyr-phosphorylation of band 3 can be triggered, inhibiting Tyr-phosphatase action and inducing erythrocyte membrane reorganization.

Gene expression patterns of chemoresistant and chemosensitive serous epithelial ovarian tumors with possible predictive value in response to initial chemotherapy.

Chemotherapy (CT) resistance in ovarian cancer is broad and encompasses diverse, unrelated drugs, suggesting more than one mechanism of resistance. We aimed to analyze the gene expression patterns in primary serous epithelial ovarian cancer (EOC) samples displaying different responses to first-line CT in an attempt to identify specific molecular signatures associated with response to CT. Initially, the expression profiles of 15 chemoresistant serous EOC tumors [time to recurrence (TTR) or =30 months) were independently analyzed which allowed the identification of specific sets of differentially expressed genes that might be functionally implicated in the evolution of the chemoresistant or the chemosensitive phenotype.

Negative sentinel lymph node accurately predicts negative status of pelvic lymph nodes in uterine cervix carcinoma.

Objective: The significance of negative sentinel lymph nodes (SLN) is important in the staging and treatment of melanoma and a few other cancers, but is controversial in uterine cervix carcinoma. Our study was aimed at correlating the SLN status in cervical carcinoma with non-sentinel lymph nodes (non-SLN), in a uniform and well controlled population.

Methods: This study includes 36 patients with stage I and IIA cervical carcinoma and bilaterally negative SLN on final pathology.

Gene expression profiling of paired ovarian tumors obtained prior to and following adjuvant chemotherapy: molecular signatures of chemoresistant tumors.

Chemotherapy (CT) resistance in ovarian cancer is related to multiple factors, and assessment of these factors is necessary for the development of new drugs and therapeutic regimens. In an effort to identify such determinants, we evaluated the expression of approximately 21,000 genes using DNA microarray screening in paired tumor samples taken prior to and after CT treatment from 6 patients with predominantly advanced stage, high-grade epithelial ovarian cancer. A subset of differentially expressed genes was selected from all microarray data by initial filtering on confidence at p=0.

Band 3 tyr-phosphorylation in normal and glucose-6-phospate dehydrogenase-deficient human erythrocytes.

Haemolysis is usually episodic in glucose-6-phosphate dehydrogenase (G6PD) deficiency, often triggered by a period of oxidative stress. In the present work, we investigate a possible biochemical mechanism underlying the enhanced susceptibility of G6PD deficient red blood cells (RBC) to oxidative stress. We analysed eight male subjects with Mediterranean glucose-6P-dehydrogenase deficiency (G6PDd), class II, for their ability in phosphorylating erythrocyte membrane band 3 following oxidative and osmotic stress.

Effector-induced Syk-mediated phosphorylation in human erythrocytes.

Band 3 (AE1), the most prominent polypeptide of the human erythrocyte membrane, becomes heavily tyrosine phosphorylated following treatment of intact cells with protein tyrosine phosphatase inhibitors such as diamide, pervanadate, vanadate, or N-ethylmaleimide (NEM). The mechanism underlying this tyrosine phosphorylation is thought to involve the sequential action of two protein tyrosine kinases, Syk (p72syk) and Lyn (p53/56lyn). While Lyn catalysed phosphorylation appears to be strictly dependent on prior phosphorylation of Tyr8 and 21 of band 3 by Syk, little is known about the mechanism of induction of Syk phosphorylation.

Human sperm express cannabinoid receptor Cb1, the activation of which inhibits motility, acrosome reaction, and mitochondrial function.

Cannabinoids and endocannabinoids negatively influence sperm functions. These substances have been demonstrated in many mammalian tissues, including male and female reproductive tracts, and previous studies have shown the presence of functional receptors for cannabinoids in human sperm. The present study, by means of RT-PCR and Western blot techniques, demonstrates that human sperm express the CB(1), but not CB(2), cannabinoid receptor (CB-R) subtype located in the head and middle piece of the sperm.