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Article ; Online: Gender susceptibility to COVID-19: a review of the putative role of sex hormones and X chromosome.

Foresta, C / Rocca, M S / Di Nisio, A

Journal of endocrinological investigation

2020 Volume 44, Issue 5, Page(s) 951–956

Abstract: Background: The recent emergence of COVID-19 poses a global health emergency. One of the most frequently reported data is sex-related severity and mortality: according to the last available analysis on 239,709 patients in Italy, lethality is 17.7% in ... ...

Abstract	Background: The recent emergence of COVID-19 poses a global health emergency. One of the most frequently reported data is sex-related severity and mortality: according to the last available analysis on 239,709 patients in Italy, lethality is 17.7% in men and 10.8% in women, with 59% of total deaths being men. Interestingly, the infection rate is lower in males than in females, with 45.8% and 54.2% of positive cases, respectively, suggesting that gender-related factor may worsen disease evolution. A tentative hypothesis to explain these findings is the role of angiotensin-converting enzyme 2 (ACE2) and serine protease TMPRSS2 involved in viral infection. Purpose: In this review, we summarize the available evidence pointing to gender-related differences in ACE2 and TMPRSS2 expression, from both genetic and endocrine points of view. Results: Altogether, available evidence points toward two not-mutually exclusive mechanisms in gender susceptibility to COVID-19 by sex hormonal regulation of ACE2 and TMPRSS2. On one hand, ACE2 expression could be increased in women, either by estrogens or constitutively by X chromosome inactivation escape or by reduced methylation, providing a larger reservoir of ACE2 to maintain the fundamental equilibrium of RAS regulatory axis. On the other, low levels of androgens in women may keep at low levels TMPRSS2 expression, representing a further protective factor for the development of COVID-19 infection, despite the increased expression of ACE2, which represents the Trojan horse for SARS-CoV-2 entry. Conclusions: Both mechanisms consistently point to the role of sex hormones and sex chromosomes in the differential severity and lethality of COVID-19 in men and women.
MeSH term(s)	Angiotensin-Converting Enzyme 2/blood ; Angiotensin-Converting Enzyme 2/genetics ; COVID-19/epidemiology ; COVID-19/genetics ; Chromosomes, Human, X/genetics ; Female ; Genetic Predisposition to Disease/epidemiology ; Gonadal Steroid Hormones ; Humans ; Male ; Serine Endopeptidases/blood ; Serine Endopeptidases/genetics ; Sex Characteristics ; Sex Factors
Chemical Substances	Gonadal Steroid Hormones ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Serine Endopeptidases (EC 3.4.21.-) ; TMPRSS2 protein, human (EC 3.4.21.-)
Keywords	covid19
Language	English
Publishing date	2020-09-16
Publishing country	Italy
Document type	Journal Article ; Review
ZDB-ID	432272-1
ISSN	1720-8386 ; 0391-4097 ; 1121-1369
ISSN (online)	1720-8386
ISSN	0391-4097 ; 1121-1369
DOI	10.1007/s40618-020-01383-6
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Article ; Online: Update on bioethical, medical and fertility issues in gender incongruence during transition age.

Conflitti, A C / Spaziani, M / Pallotti, F / Tarsitano, M G / Di Nisio, A / Paoli, D / Lombardo, F

Journal of endocrinological investigation

2023 Volume 46, Issue 9, Page(s) 1725–1736

Abstract: Purpose: Many issues still remain unresolved in the management of pubertal patients with gender incongruence (GI). The aim of this review is to discuss the main aspects of the treatment of these patients to provide a practical approach for clinicians.!## ...

Abstract	Purpose: Many issues still remain unresolved in the management of pubertal patients with gender incongruence (GI). The aim of this review is to discuss the main aspects of the treatment of these patients to provide a practical approach for clinicians. Methods: A comprehensive literature search within PubMed was performed to provide updates of available evidence regarding the impact on bioethical, medical and fertility issues in gender incongruence during transition age. Results: Gender Affirming Hormone Treatment (GAHT) and Gender Affirming Surgery (GAS) can induce unsatisfaction with change, future regrets, and the risk of infertility. This raises ethical issues especially in the management of pubertal patients that remain unresolved. Therapy with GnRH analogues (GnRHa) is intended to delay puberty, so as to give the adolescent a longer period of time to decide whether to continue with the treatments. At the level of physical changes, this therapy may have an effect on bone mineralization and body composition; however, long-term longitudinal data are not yet available. An important feature related to the use of GnRHa is the risk of fertility. Gamete cryopreservation is the most established method of fertility preservation (FP) and should be counselled to transgender adolescents. However, these patients are not always interested in having biological children. Conclusion: Based on the current evidence, there is a need to conduct further research to clarify certain issues and to standardize clinical practice and improve counselling in transgender adolescent decision making and avoid regrets in the future.
MeSH term(s)	Child ; Adolescent ; Humans ; Fertility Preservation ; Counseling ; Infertility ; Cryopreservation ; Transsexualism ; Transgender Persons ; Gender Dysphoria/drug therapy ; Gender Identity
Language	English
Publishing date	2023-04-18
Publishing country	Italy
Document type	Journal Article ; Review
ZDB-ID	432272-1
ISSN	1720-8386 ; 0391-4097 ; 1121-1369
ISSN (online)	1720-8386
ISSN	0391-4097 ; 1121-1369
DOI	10.1007/s40618-023-02077-5
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Article: Gender susceptibility to COVID-19: a review of the putative role of sex hormones and X chromosome

Foresta, C / Rocca, M S / Di Nisio, A

J. endocrinol. invest

Abstract: BACKGROUND: The recent emergence of COVID-19 poses a global health emergency. One of the most frequently reported data is sex-related severity and mortality: according to the last available analysis on 239,709 patients in Italy, lethality is 17.7% in men ...

Abstract	BACKGROUND: The recent emergence of COVID-19 poses a global health emergency. One of the most frequently reported data is sex-related severity and mortality: according to the last available analysis on 239,709 patients in Italy, lethality is 17.7% in men and 10.8% in women, with 59% of total deaths being men. Interestingly, the infection rate is lower in males than in females, with 45.8% and 54.2% of positive cases, respectively, suggesting that gender-related factor may worsen disease evolution. A tentative hypothesis to explain these findings is the role of angiotensin-converting enzyme 2 (ACE2) and serine protease TMPRSS2 involved in viral infection. PURPOSE: In this review, we summarize the available evidence pointing to gender-related differences in ACE2 and TMPRSS2 expression, from both genetic and endocrine points of view. RESULTS: Altogether, available evidence points toward two not-mutually exclusive mechanisms in gender susceptibility to COVID-19 by sex hormonal regulation of ACE2 and TMPRSS2. On one hand, ACE2 expression could be increased in women, either by estrogens or constitutively by X chromosome inactivation escape or by reduced methylation, providing a larger reservoir of ACE2 to maintain the fundamental equilibrium of RAS regulatory axis. On the other, low levels of androgens in women may keep at low levels TMPRSS2 expression, representing a further protective factor for the development of COVID-19 infection, despite the increased expression of ACE2, which represents the Trojan horse for SARS-CoV-2 entry. CONCLUSIONS: Both mechanisms consistently point to the role of sex hormones and sex chromosomes in the differential severity and lethality of COVID-19 in men and women.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #763952
Database	COVID19

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Article ; Online: Gender susceptibility to COVID-19

Foresta, C. / Rocca, M. S. / Di Nisio, A.

Journal of Endocrinological Investigation ; ISSN 1720-8386

a review of the putative role of sex hormones and X chromosome

2020

Abstract: Abstract Background The recent emergence of COVID-19 poses a global health emergency. One of the most frequently reported data is sex-related severity and mortality: according to the last available analysis on 239,709 patients in Italy, lethality is 17.7% ...

Abstract	Abstract Background The recent emergence of COVID-19 poses a global health emergency. One of the most frequently reported data is sex-related severity and mortality: according to the last available analysis on 239,709 patients in Italy, lethality is 17.7% in men and 10.8% in women, with 59% of total deaths being men. Interestingly, the infection rate is lower in males than in females, with 45.8% and 54.2% of positive cases, respectively, suggesting that gender-related factor may worsen disease evolution. A tentative hypothesis to explain these findings is the role of angiotensin-converting enzyme 2 (ACE2) and serine protease TMPRSS2 involved in viral infection. Purpose In this review, we summarize the available evidence pointing to gender-related differences in ACE2 and TMPRSS2 expression, from both genetic and endocrine points of view. Results Altogether, available evidence points toward two not-mutually exclusive mechanisms in gender susceptibility to COVID-19 by sex hormonal regulation of ACE2 and TMPRSS2. On one hand, ACE2 expression could be increased in women, either by estrogens or constitutively by X chromosome inactivation escape or by reduced methylation, providing a larger reservoir of ACE2 to maintain the fundamental equilibrium of RAS regulatory axis. On the other, low levels of androgens in women may keep at low levels TMPRSS2 expression, representing a further protective factor for the development of COVID-19 infection, despite the increased expression of ACE2, which represents the Trojan horse for SARS-CoV-2 entry. Conclusions Both mechanisms consistently point to the role of sex hormones and sex chromosomes in the differential severity and lethality of COVID-19 in men and women.
Keywords	Endocrinology, Diabetes and Metabolism ; Endocrinology ; covid19
Language	English
Publisher	Springer Science and Business Media LLC
Publishing country	us
Document type	Article ; Online
DOI	10.1007/s40618-020-01383-6
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Article ; Online: Risk factors on testicular function in adolescents.

Cargnelutti, F / Di Nisio, A / Pallotti, F / Spaziani, M / Tarsitano, M G / Paoli, D / Foresta, C

Journal of endocrinological investigation

2022 Volume 45, Issue 9, Page(s) 1625–1639

Abstract: Purpose: Adolescence represents an important window for gonadal development. The aim of this review is to carry out a critical excursus of the most recent literature on endogenous and exogenous risk factors related to testicular function, focusing the ... ...

Abstract	Purpose: Adolescence represents an important window for gonadal development. The aim of this review is to carry out a critical excursus of the most recent literature on endogenous and exogenous risk factors related to testicular function, focusing the research on adolescence period. Methods: A comprehensive literature search within PubMed was performed to provide a summary of currently available evidence regarding the impact on adolescence of varicocele, cryptorchidism, cancer, diabetes, lifestyle factors, endocrine disruptors, obesity and sexually transmitted diseases. We focused on human studies that evaluated a possible impact of these factors on puberty timing and their effects on andrological health. Results: Evidence collected seems to suggest that andrological health in adolescence may be impaired by several factors, as varicocele, cryptorchidism, and childhood cancer. Despite an early diagnosis and treatment, many adolescents might still have symptoms and sign of a testicular dysfunction in their adult life and at the current time it is not possible to predict which of them will experience andrological problems. Lifestyle factors might have a role in these discrepancies. Most studies point out towards a correlation between obesity, insulin resistance, alcohol, smoking, use of illegal drugs and testicular function in pubertal boys. Also, endocrine disruptors and sexually transmitted diseases might contribute to impair reproductive health, but more studies in adolescents are needed. Conclusion: According to currently available evidence, there is an emerging global adverse trend of high-risk and unhealthy behaviors in male adolescents. A significant proportion of young men with unsuspected and undiagnosed andrological disorders engage in behaviors that could impair testicular development and function, with an increased risk for later male infertility and/or hypogonadism during the adult life. Therefore, adolescence should be considered a key time for intervention and prevention of later andrological diseases.
MeSH term(s)	Adolescent ; Adult ; Child ; Cryptorchidism ; Endocrine Disruptors/adverse effects ; Humans ; Male ; Obesity/complications ; Risk Factors ; Testis ; Varicocele
Chemical Substances	Endocrine Disruptors
Language	English
Publishing date	2022-03-14
Publishing country	Italy
Document type	Journal Article ; Review
ZDB-ID	432272-1
ISSN	1720-8386 ; 0391-4097 ; 1121-1369
ISSN (online)	1720-8386
ISSN	0391-4097 ; 1121-1369
DOI	10.1007/s40618-022-01769-8
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Article ; Online: RS 2247911 polymorphism of GPRC6A gene and serum undercarboxylated-osteocalcin are associated with testis function.

Jawich, K / Rocca, M Santa / Al Fahoum, S / Alhalabi, M / Di Nisio, A / Foresta, C / Ferlin, A / De Toni, L

Journal of endocrinological investigation

2022 Volume 45, Issue 9, Page(s) 1673–1682

Abstract: Purpose: Undercarboxylated-Osteocalcin (ucOCN), acting on its putative receptor GPRC6A, was shown to stimulate testosterone (T) production by Leydig cells in rodents, in parallel with the hypothalamus-pituitary-gonadal axis (HPG) mediated by luteinizing ...

Abstract	Purpose: Undercarboxylated-Osteocalcin (ucOCN), acting on its putative receptor GPRC6A, was shown to stimulate testosterone (T) production by Leydig cells in rodents, in parallel with the hypothalamus-pituitary-gonadal axis (HPG) mediated by luteinizing hormone (LH). The aim of this cross-sectional study was to evaluate the association among serum ucOCN, rs2247911 polymorphism of GPRC6A gene and the endocrine/semen pattern in a cohort of infertile males, possibly identifying an involvement of the ucOCN-GPRC6A axis on testis function. Methods: 190 males, including 74 oligozoospermic subjects, 58 azoosperminc patients and 58 normozoospermic controls, were prospectively recruited at the Orient Hospital for Infertility, Assisted Reproduction and Genetics in Syria (Study N. 18FP), from July 2018 to June 2020. Outpatient evaluation included the clinical history, anthropometrics and a fasting blood sampling for hormonals, serum OCN (both carboxylated and undercarboxylated), glycemic and lipid profile and screening for rs2247911 GPRC6A gene polymorphism. Results: Higher serum ucOCN associated with higher T and HDL-cholesterol (respectively: r = 0.309, P < 0.001 and r = 0.248, P = 0.001), and with lower FSH (r = - 0.327, P < 0.001) and LDL-cholesterol (r = - 0.171; P = 0.018). Patients bearing the GG genotype of rs2247911 had higher sperm count compared to GA genotype (P = 0.043) and, compared to both AG and AA genotypes, had higher serum T (P = 0.004, P = 0.001) and lower triglycerides levels (P = 0.002, P < 0.001). Upon normalization for LH levels and body mass index, rs2274911 and ucOCN were significantly associated with higher serum T at linear stepwise regression analysis (P = 0.013, P = 0.007). Conclusions: Our data suggest the involvement of ucOCN-GPRC6A axis in the regulation of T production by the testis, subsidiary to HPG.
MeSH term(s)	Cholesterol/blood ; Cross-Sectional Studies ; Humans ; Male ; Osteocalcin/blood ; Polymorphism, Genetic ; Receptors, G-Protein-Coupled/genetics ; Semen/metabolism ; Testis/metabolism ; Testosterone
Chemical Substances	GPRC6A protein, human ; Receptors, G-Protein-Coupled ; Osteocalcin (104982-03-8) ; Testosterone (3XMK78S47O) ; Cholesterol (97C5T2UQ7J)
Language	English
Publishing date	2022-04-28
Publishing country	Italy
Document type	Journal Article
ZDB-ID	432272-1
ISSN	1720-8386 ; 0391-4097 ; 1121-1369
ISSN (online)	1720-8386
ISSN	0391-4097 ; 1121-1369
DOI	10.1007/s40618-022-01803-9
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Article ; Online: Photoplethysmography Signal Wavelet Enhancement and Novel Features Selection for Non-Invasive Cuff-Less Blood Pressure Monitoring.

Attivissimo, Filippo / De Palma, Luisa / Di Nisio, Attilio / Scarpetta, Marco / Lanzolla, Anna Maria Lucia

Sensors (Basel, Switzerland)

2023 Volume 23, Issue 4

Abstract: In this paper, new features relevant to blood pressure (BP) estimation using photoplethysmography (PPG) are presented. A total of 195 features, including the proposed ones and those already known in the literature, have been calculated on a set composed ... ...

Abstract	In this paper, new features relevant to blood pressure (BP) estimation using photoplethysmography (PPG) are presented. A total of 195 features, including the proposed ones and those already known in the literature, have been calculated on a set composed of 50,000 pulses from 1080 different patients. Three feature selection methods, namely Correlation-based Feature Selection (CFS), RReliefF and Minimum Redundancy Maximum Relevance (MRMR), have then been applied to identify the most significant features for BP estimation. Some of these features have been extracted through a novel PPG signal enhancement method based on the use of the Maximal Overlap Discrete Wavelet Transform (MODWT). As a matter of fact, the enhanced signal leads to a reliable identification of the characteristic points of the PPG signal (e.g., systolic, diastolic and dicrotic notch points) by simple means, obtaining results comparable with those from purposely defined algorithms. For systolic points, mean and std of errors computed as the difference between the locations obtained using a purposely defined already known algorithm and those using the MODWT enhancement are, respectively, 0.0097 s and 0.0202 s; for diastolic points they are, respectively, 0.0441 s and 0.0486 s; for dicrotic notch points they are 0.0458 s and 0.0896 s. Hence, this study leads to the selection of several new features from the MODWT enhanced signal on every single pulse extracted from PPG signals, in addition to features already known in the literature. These features can be employed to train machine learning (ML) models useful for estimating systolic blood pressure (
MeSH term(s)	Humans ; Blood Pressure ; Photoplethysmography ; Algorithms ; Diastole ; Heart Rate
Language	English
Publishing date	2023-02-19
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2052857-7
ISSN	1424-8220 ; 1424-8220
ISSN (online)	1424-8220
ISSN	1424-8220
DOI	10.3390/s23042321
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Article ; Online: Battery Testing and Discharge Model Validation for Electric Unmanned Aerial Vehicles (UAV).

Di Nisio, Attilio / Avanzini, Giulio / Lotano, Daniel / Stigliano, Donato / Lanzolla, Anna M L

Sensors (Basel, Switzerland)

2023 Volume 23, Issue 15

Abstract: Electrical engines are becoming more common than thermal ones. Therefore, there is an increasing interest in the characterization of batteries and in measuring their state of charge, as an overestimation would cause the vehicle to run out of energy and ... ...

Abstract	Electrical engines are becoming more common than thermal ones. Therefore, there is an increasing interest in the characterization of batteries and in measuring their state of charge, as an overestimation would cause the vehicle to run out of energy and an underestimation means that the vehicle is running in suboptimal conditions. This is of paramount importance for flying vehicles, as their endurance decreases with the increase in weight. This work aims at finding a novel empirical model for the discharge curve of an arbitrary number of battery pack cells, that uses as few tunable parameters as possible and hence is easy to adapt for every single battery pack needed by the operator. A suitable measurement setup for battery tests, which includes voltage and current sensors, has been developed and described. Tests are performed on both constant and variable power loads to investigate different real-world scenarios that are easy to reproduce. The main achievement of this novel model is indeed the ability to predict discharges at variable power based on a preliminary characterization performed at constant power. This leads to the possibility of rapidly tuning the model for each battery with promising accuracy. The results will show that the predicted discharged capacities of the model have a normalized error below 0.7%.
Language	English
Publishing date	2023-08-04
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2052857-7
ISSN	1424-8220 ; 1424-8220
ISSN (online)	1424-8220
ISSN	1424-8220
DOI	10.3390/s23156937
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Article: Editorial: Emerging Chemical Risks for Human Health: Endocrine Disruption by Per- and Poly-Fluorinated Alkyl Substances (PFAS).

Di Nisio, Andrea / Lopez-Espinosa, Maria-Jose / Foresta, Carlo

Frontiers in endocrinology

2022 Volume 12, Page(s) 813785

Language	English
Publishing date	2022-01-12
Publishing country	Switzerland
Document type	Editorial ; Introductory Journal Article
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2021.813785
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Article ; Online: Water and soil pollution as determinant of water and food quality/contamination and its impact on male fertility.

Di Nisio, Andrea / Foresta, Carlo

Reproductive biology and endocrinology : RB&E

2019 Volume 17, Issue 1, Page(s) 4

Abstract: Over the past two decades, public health has focused on the identification of environmental chemical factors that are able to adversely affect hormonal function, known as endocrine disruptors (EDs). EDs mimic naturally occurring hormones like estrogens ... ...

Abstract	Over the past two decades, public health has focused on the identification of environmental chemical factors that are able to adversely affect hormonal function, known as endocrine disruptors (EDs). EDs mimic naturally occurring hormones like estrogens and androgens which can in turn interfere with the endocrine system. As a consequence, EDs affect human reproduction as well as post and pre-natal development. In fact, infants can be affected already at prenatal level due to maternal exposure to EDs. In particular, great attention has been given to those chemicals, or their metabolites, that have estrogenic properties or antagonistic effects on the activity of androgen or even inhibiting their production. These compounds have therefore the potential of interfering with important physiological processes, such as masculinization, morphological development of the urogenital system and secondary sexual traits. Animal and in vitro studies have supported the conclusion that endocrine-disrupting chemicals affect the hormone-dependent pathways responsible for male gonadal development, either through direct interaction with hormone receptors or via epigenetic and cell-cycle regulatory modes of action. In human populations, epidemiological studies have reported an overall decline of male fertility and an increased incidence of diseases or congenital malformations of the male reproductive system. The majority of studies point towards an association between exposure to EDs and male and/or female reproductive system disorders, such as infertility, endometriosis, breast cancer, testicular cancer, poor sperm quality and/or function. Despite promising discoveries, a causal relationship between the reproductive disorders and exposure to specific toxicants has yet to be established, due to the complexity of the clinical protocols used, the degree of occupational or environmental exposure, the determination of the variables measured and the sample size of the subjects examined. Despite the lack of consistency in the results of so many studies investigating endocrine-disrupting properties of many different classes of chemicals, the overall conclusion points toward a positive association between exposure to EDs and reproductive system. Future studies should focus on a uniform systems to examine human populations with regard to the exposure to specific EDs and the direct effect on the reproductive system.
MeSH term(s)	Endocrine Disruptors/analysis ; Endocrine Disruptors/toxicity ; Environmental Exposure ; Environmental Pollutants/analysis ; Environmental Pollutants/toxicity ; Food Contamination ; Food Quality ; Humans ; Infertility, Male/epidemiology ; Infertility, Male/etiology ; Male ; Observational Studies as Topic ; Semen/drug effects ; Sexual Development/drug effects
Chemical Substances	Endocrine Disruptors ; Environmental Pollutants
Language	English
Publishing date	2019-01-06
Publishing country	England
Document type	Journal Article ; Review
ISSN	1477-7827
ISSN (online)	1477-7827
DOI	10.1186/s12958-018-0449-4
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