Zinc as a Drug for Wilson's Disease, Non-Alcoholic Liver Disease and COVID-19-Related Liver Injury.

Zinc is the second most abundant trace element in the human body, and it plays a fundamental role in human physiology, being an integral component of hundreds of enzymes and transcription factors. The discovery that zinc atoms may compete with copper for their absorption in the gastrointestinal tract let to introduce zinc in the therapy of Wilson's disease, a congenital disorder of copper metabolism characterized by a systemic copper storage. Nowadays, zinc salts are considered one of the best therapeutic approach in patients affected by Wilson's disease. On the basis of the similarities, at histological level, between Wilson's disease and non-alcoholic liver disease, zinc has been successfully introduced in the therapy of non-alcoholic liver disease, with positive effects both on insulin resistance and oxidative stress. Recently, zinc deficiency has been indicated as a possible factor responsible for the susceptibility of elderly patients to undergo infection by SARS-CoV-2, the coronavirus responsible for the COVID-19 pandemic. Here, we present the data correlating zinc deficiency with the insurgence and progression of Covid-19 with low zinc levels associated with severe disease states. Finally, the relevance of zinc supplementation in aged people at risk for SARS-CoV-2 is underlined, with the aim that the zinc-based drug, classically used in the treatment of copper overload, might be recorded as one of the tools reducing the mortality of COVID-19, particularly in elderly people.

The Selective Interaction of Pistacia lentiscus Oil vs. Human Streptococci, an Old Functional Food Revisited with New Tools.

Pistacia lentiscus berry oil (LBO) represents a typical vegetal product of the Mediterranean basin that has been formally used in traditional cuisine for 100s of years. In addition to its interesting alimentary properties, this product could represent an interesting candidate in the field of research on the study of new anti-infective agents. In fact, in Mediterranean countries, lentisk oil still continues to be widely used in folk medicine for oral and skin affections, in particular, acute gingivitis, pediatric skin infections such as impetigo and foot plaques, and biofilm related infections often associated with Streptococcus spp. Following these observations, we have hypothesized a "lentisk oil-bacteria" interaction, placing particular emphasis on the different Streptococcal species involved in these oral and skin diseases. In accordance with this hypothesis, the use of standard antimicrobial-antibiofilm methods (MIC, MBC, MBIC) allowed the interesting behavior of these bacteria to be observed and, in this context, the response to lentisk oil appears to be correlated with the pathogenic profile of the considered microorganism. Two probiotic strains of S. salivarius K12/M18 appeared to be non-sensitive to this product, while a set of five different pathogenic strains (S. agalactiae, S. intermedius, S. mitis, S. mutans, S. pyogenes) showed a response that was correlated to the fatty acid metabolic pathway of the considered species. In fact, at different times of bacteria development, selective High Performance Liquid Chromatography analysis of the growth medium containing LBO detected a significant increase in free unsaturated fatty acids (UFAs) in particular oleic, palmitic and linoleic acids, which are already known for their antibacterial activity. In this context, we have hypothesized that LBO could be able to modulate the pathogen/probiotic rate in a Streptococcal population using the fatty acid metabolic pathway to help the probiotic strain. This hypothesis was strengthened by performing antibacterial testing with oleic acid and an in silico evaluation of the Streptococcal MCRA protein, an enzyme involved in the production of saturated fatty acids from UFA. These results show that LBO may have been used in ancient times as a "natural microbial modulating extract" in the prevention of biofilm- associated diseases.

Soluble CD14 subtype (sCD14-ST) presepsin in premature and full term critically ill newborns with sepsis and SIRS.

Neonatal sepsis still remains a major cause of morbidity and mortality in neonatal intensive care unit (NICU). Recently, soluble CD14 subtype (sDC14-ST) also named presepsin, was proposed as an effective biomarker for diagnosing, monitoring, and assessing the risk of neonatal sepsis and septic shock. The aim of this study was to investigate the diagnostic accuracy of sCD14-ST presepsin in diagnosing neonatal bacterial sepsis and in discriminating non-bacterial systemic inflammatory response syndrome (SIRS) from bacterial sepsis. This study involved 65 critically ill full-term and preterm newborns admitted to the neonatal intensive care unit (NICU), divided into three groups: 25 newborns with bacterial neonatal sepsis (group A); 15 newborns with a diagnosis of non-bacterial SIRS and with no localizing source of bacterial infection (group B); and 25 babies with no clinical or bacteriological signs of systemic or local infection receiving routine NICU care, most of them treated with phototherapy for neonatal jaundice (group C). A total of 102 whole blood samples were collected, 40 in group A, 30 in group B and 32 in group C. In 10 babies included in group A, sCD14-ST presepsin was also measured in an additional second blood sample collected 3 days after the start of antibiotic treatment. sCD14-ST presepsin was measured by a commercially available chemiluminescent enzyme immunoassay (CLEIA) optimized on an automated immunoassay analyzer. Statistical analysis was performed by means of MedCalc® statistical package; receiver operating characteristic (ROC) analysis was computed, and the area under the ROC curve (AUC) was used to evaluate the ability of sCD14-ST to discriminate neonatal bacterial sepsis from non-bacterial SIRS. Blood sCD14-ST presepsin levels were found significantly higher in bacterial sepsis when compared with controls (p<0.0001); similarly, they were higher in non-bacterial SIRS when compared with controls (p<0.0001). However, no statistically significant difference was found between bacterial sepsis and non-bacterial SIRS (p=0.730). In our population, CRP and sCD14-ST did not correlate with each other. ROC analysis revealed that sCD14-ST presepsin has an area under the curve (AUC) of 0.995 (95% C.I.: 0.941-1.00) greater than that of CRP (0.827; 95% C.I.: 0.72-0.906). Similarly, in the group of babies with non-infectious SIRS, sCD14-ST AUC was greater than CRP AUC (0.979; 95% C.I.: 0.906-0.999 versus 0.771; 95% C.I.: 0.647-0.868). In controls, preliminary reference intervals for sCD14-ST ranged 223.4-599.7 ng/L, being significantly different from those previously published elsewhere. In conclusion, sCD14-ST presepsin could be introduced in clinical practice as a diagnostic tool for improving the management of neonatal sepsis and non-bacterial SIRS.

Observational study on the efficacy of the supplementation with a preparation with several minerals and vitamins in improving mood and behaviour of healthy puerperal women.

We investigated whether a formulation containing vitamins and minerals (vit&min) could improve the worsening of mood changes occurring after delivery ("a.d."). The study was performed in 552 healthy non-anaemic puerperal women ("p.w") without risk factors for puerperal depression ("p.d"). They were at their first full-term pregnancy, and spontaneously delivered healthy newborns. The Edinburgh Depression Postnatal scale (EPDS) evaluates the psychological status of "p.w". EPDS was administered the 3rd (visit 1), 15th (visit 2) and 30th (visit 3) day "a.d.". An EPDS >12 indicates a major susceptibility to "p.d". At the same time intervals, haemoglobin, iron and ferritin (haematological parameters) levels were evaluated. After visit 1, the subjects were randomized to vit&min treatment (group A; N.274) or to calcium/vitamin D3 treatment (group B; N.278). In both groups haematological parameters significantly increased without differences between the groups. EPDS score improved in both groups, but in the group A, the EPDS decrease was significantly larger (p < 0.05) in comparison to the group B. This effect is mainly evident in subjects with a basal EPDS ≥ 12. An early examination of psychological condition could select "p.w." with a high susceptibility to neuronal changes occurring postpartum. Vit&min favourably modulates brain functions antagonizing the evolution to "p.d".

Early prediction of hypocalcemia following total thyroidectomy using combined intact parathyroid hormone and serum calcium measurement.

BACKGROUNDS: Concomitant intact parathyroid hormone (iPTH) and serum calcium measurement is deemed to be useful in predicting hypocalcemia after total thyroidectomy. This study aimed to prospectively assess the diagnostic accuracy of combined iPTH and serum calcium measurement in predicting early postoperative hypocalcemia. METHODS: From January 2010 to January 2011, 112 patients underwent total thyroidectomy in our department. A prospective study was carried out to search for factors predicting postoperative hypocalcemia. Serum calcium, phosphorus, and iPTH levels have been measured before operation and at 6, 24, and 48 h postoperatively. Hypocalcemia was defined as a serum calcium level less than 8.0 mg/dL. Sensitivity and specificity of different serum measurements have been calculated using the receiver-operator characteristics curve. RESULTS: Thirty-three patients (29.5 %) had transient postoperative hypocalcemia. Serum iPTH level showed the highest sensitivity and specificity in predicting hypocalcemia after 6 h (84.8 % and 93.7 %, respectively) for a criterion value ≤ 12.1 pg/mL. Serum calcium level showed the highest sensitivity and specificity after 24 h (93.9 and 100.0 %, respectively) for a criterion value ≤ 7.97 mg/dL. Combined cutoffs of 6-h iPTH and 24-h serum calcium showed sensitivity and specificity of 100.0 %. CONCLUSIONS: The combined measurement of 6-h iPTH and 24-h serum calcium are highly predictive of early postoperative hypocalcemia. Patients with serum iPTH and calcium level ≤ criterion value are at major risk for developing hypocalcemia. These results are important in selecting patients eligible for early discharge and those patients who need calcium and vitamin D supplementation.

The role of the laboratory in choosing antibiotics.

OBJECTIVE: Antimicrobial resistance is one of the biggest problem in medicine at the beginning of the third millennium. Antibiotic resistance is frequently associated with significant morbidity, longer hospitalization, excess costs and mortality. METHODS: In this work we discussed the role of clinical microbiology laboratory as an essential part for an effective infection control program, especially in management and treatment of "difficult infections". RESULTS: At present time, laboratory personnel have a broad range of new technologies that they can use to support and enhance the efforts of the infection control staff. In addition a network of established experts in the determination of antimicrobial breakpoints and in antimicrobial susceptibility testing has been constituted in Europe under the auspices of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and the European Centre for Disease Prevention and Control (ECDC). CONCLUSION: Qualified personnel and new strategies to overcome drug resistance can contribute to solve the microbial infections problems.