“Bridging the Gap” Everything that Could Have Been Avoided If We Had Applied Gender Medicine, Pharmacogenetics and Personalized Medicine in the Gender-Omics and Sex-Omics Era

Gender medicine is the first step of personalized medicine and patient-centred care, an essential development to achieve the standard goal of a holistic approach to patients and diseases. By addressing the interrelation and integration of biological markers (i.e., sex) with indicators of psychological/cultural behaviour (i.e., gender), gender medicine represents the crucial assumption for achieving the personalized health-care required in the third millennium. However, ‘sex’ and ‘gender’ are often misused as synonyms, leading to frequent misunderstandings in those who are not deeply involved in the field. Overall, we have to face the evidence that biological, genetic, epigenetic, psycho-social, cultural, and environmental factors mutually interact in defining sex/gender differences, and at the same time in establishing potential unwanted sex/gender disparities. Prioritizing the role of sex/gender in physiological and pathological processes is crucial in terms of efficient prevention, clinical signs’ identification, prognosis definition, and therapy optimization. In this regard, the omics-approach has become a powerful tool to identify sex/genderspecific disease markers, with potential benefits also in terms of socio-psychological wellbeing for each individual, and cost-effectiveness for National Healthcare systems. “Being a male or being a female” is indeed important from a health point of view and it is no longer possible to avoid “sex and gender lens” when approaching patients. Accordingly, personalized healthcare must be based on evidence from targeted research studies aimed at understanding how sex and gender influence health across the entire life span. The rapid development of genetic tools in the molecular medicine approaches and their impact in healthcare is an example of highly specialized applications that have moved from specialists to primary care providers (e.g., pharmacogenetic and pharmacogenomic applications in routine medical practice). Gender medicine needs to follow the same path and become an established medical approach. To face the genetic, molecular and pharmacological bases of the existing sex/gender gap by means of omics approaches will pave the way to the discovery and identification of novel drug-targets/therapeutic protocols, personalized laboratory tests and diagnostic procedures (sex/gender-omics). In this scenario, the aim of the present review is not to simply resume the state-of-the-art in the field, rather an opportunity to gain insights into gender medicine, spanning from molecular up to social and psychological stances. The description and critical discussion of some key selected multidisciplinary topics considered as paradigmatic of sex/gender differences and sex/gender inequalities will allow to draft and design strategies useful to fill the existing gap and move forward

A Movement-Tremors Recorder for Patients of Neurodegenerative Diseases

Neurodegenerative diseases such as Alzheimer, Parkinson, motor neuron, and Chorea affect millions of people today. Their effect on the central nervous system causes the loss of brain functions as well as motor disturbances and sometimes cognitive deficits. In such a scenario, the monitoring and evaluation of early symptoms are mandatory for the improvement of the patient's quality of life. Here, the authors describe the development, the laboratory calibration, and the "in-field validation" under the medical supervision of a movement tremors recorder for subjects affected by neurodegenerative diseases. The developed device is based on an array of four accelerometers connected to an embedded development board. This system is able to monitor tremor/movement, accidental falls, and, moreover, it can track the Alzheimer subjects' geographical position. A remote supervisor can collect data from the system through Bluetooth, Wi-Fi, or GSM connections. A data compression algorithm was developed directly on board in order to increase the efficiency of data transmission and reduce power consumptions

A High Performance Gel Filtration Chromatography Method for gamma-Glutamyltransferase Fraction Analysis

The clinical relevance of serum c-glutamyltransferase (GGT) activity, in areas other than hepatic function, has recently been increased by several epidemiological associations. Still, GGT remains a nonspecific test because of the influence of various pathophysiological factors. We devised a procedure based on gel filtration chromatography, followed by postcolumn injection of fluorescent GGT substrate (cglutamyl- 7-amido-4-methylcoumarin), permitting the quantification of GGT fractions in serum or plasma. Plasma GGT molecular weight distribution was analyzed in healthy volunteers (20 males; mean ± SD age 38 ± 10 years; 20 females; age 44 ± 13; total GGT 21 ± 11 for males vs 13 ± 7 for females; P < 0.01). The method is highly sensitive (determination limit: 0.5 U GGT/L), with a linear dynamic range between 0.5 and 150 U/L for each fraction. Four GGT fractions of different molecular weight were detected in all subjects of both genders: b-GGT, m-GGT, s-GGT (likely lipoprotein-bound, molecular masses >2000, 940, and 140 kDa, respectively), and a free fraction (f-GGT, 70 kDa). f-GGT and s-GGT were the main fractions in subjects with lower and higher total GGT activity, respectively. Higher total GGT activity in males is related mainly to f-GGT (P < 0.01). GGT fraction analysis may increase the sensitivity and specificity of the GGT activity test

A compact monitoring system for patients affected by neurodegenerative diseases

In this paper we report about the development of a compact monitoring system for people affected by neurodegenerative diseases as Parkinson and Alzheimer. The electronic interface is based on a Linkit ONE development board, and it is equipped with an array of up to four ADXL345 accelerometers. By considering the main symptoms of Parkinson subjects, it is possible to monitor tremors/movements and accidental falls of people wearing the system and to send data to a supervisor by Wi-Fi, Bluetooth and GSM connections. Furthermore, the geo-tagging functions, developed by means of a GPS feature, already equipped in the board, allow the monitoring of the movements and the position of Alzheimer subjects, avoiding the lost for memory failures

A movement monitoring system for patients of neurodegenerative diseases

Parkinson, Alzheimer, Koreas and motor neuron disease affect today millions of people. These neurodegenerative diseases act on central nervous system causing the loss of brain functions as well as motor disturbances and sometimes cognitive deficits. In such scenario, monitor early symptoms is mandatory. Here the authors describe the development of a monitoring system for Parkinson subjects and other patients affected by neurodegenerative diseases. The developed device is based on an array of four accelerometers connected to an embedded development board. This system is able to monitor tremor/movement, accidental falls and, moreover, it can track the Alzheimer subjects' geographical position. A remote supervisor can collect data from the system through Bluetooth, Wi-Fi or GSM connections

COVID-19 and Individual Genetic Susceptibility/Receptivity: Role of ACE1/ACE2 Genes, Immunity, Inflammation and Coagulation. Might the Double X-chromosome in Females Be Protective against SARS-CoV-2 Compared to the Single X-Chromosome in Males?

In December 2019, a novel severe acute respiratory syndrome (SARS) from a new coronavirus (SARS-CoV-2) was recognized in the city of Wuhan, China. Rapidly, it became an epidemic in China and has now spread throughout the world reaching pandemic proportions. High mortality rates characterize SARS-CoV-2 disease (COVID-19), which mainly affects the elderly, causing unrestrained cytokines-storm and subsequent pulmonary shutdown, also suspected micro thromboembolism events. At the present time, no specific and dedicated treatments, nor approved vaccines, are available, though very promising data come from the use of anti-inflammatory, anti-malaria, and anti-coagulant drugs. In addition, it seems that males are more susceptible to SARS-CoV-2 than females, with males 65% more likely to die from the infection than females. Data from the World Health Organization (WHO) and Chinese scientists show that of all cases about 1.7% of women who contract the virus will die compared with 2.8% of men, and data from Hong Kong hospitals state that 32% of male and 15% of female COVID-19 patients required intensive care or died. On the other hand, the long-term fallout of coronavirus may be worse for women than for men due to social and psychosocial reasons. Regardless of sex- or gender-biased data obtained from WHO and those gathered from sometimes controversial scientific journals, some central points should be considered. Firstly, SARS-CoV-2 has a strong interaction with the human ACE2 receptor, which plays an essential role in cell entry together with transmembrane serine protease 2 (TMPRSS2); it is interesting to note that the ACE2 gene lays on the X-chromosome, thus allowing females to be potentially heterozygous and differently assorted compared to men who are definitely hemizygous. Secondly, the higher ACE2 expression rate in females, though controversial, might ascribe them the worst prognosis, in contrast with worldwide epidemiological data. Finally, several genes involved in inflammation are located on the X-chromosome, which also contains high number of immune-related genes responsible for innate and adaptive immune responses to infection. Other genes, out from the RAS-pathway, might directly or indirectly impact on the ACE1/ACE2 balance by influencing its main actors (e.g., ABO locus, SRY, SOX3, ADAM17). Unexpectedly, the higher levels of ACE2 or ACE1/ACE2 rebalancing might improve the outcome of COVID-19 in both sexes by reducing inflammation, thrombosis, and death. Moreover, X-heterozygous females might also activate a mosaic advantage and show more pronounced sex-related differences resulting in a sex dimorphism, further favoring them in counteracting the progression of the SARS-CoV-2 infection

Experimental validation of a high accuracy test of the equivalence principle with the small satellite "Galileo galilet"

The small satellite "Galileo Galilei" (GG) has been designed to test the equivalence principle (EP) to 10(-17) with a total mass at launch of 250 kg. The key instrument is a di. fferential accelerometer made up of weakly coupled coaxial, concentric test cylinders rapidly spinning around the symmetry axis and sensitive in the plane perpendicular to it, lying at a small inclination from the orbit plane. The whole spacecraft spins around the same symmetry axis so as to be passively stabilized. The test masses are large (10 kg each, to reduce thermal noise), their coupling is very weak (for high sensitivity to differential effects), and rotation is fast (for high frequency modulation of the signal). A 1g version of the accelerometer ("Galileo Galilei on the Ground"-GGG) has been built to the full scale-except for coupling, which cannot be as weak as in the absence of weight, and a motor to maintain rotation (not needed in space due to angular momentum conservation). GGG has proved: (i) high Q; (ii) auto-centering and long term stability; (iii) a sensitivity to EP testing which is close to the target sensitivity of the GG experiment provided that the physical properties of the experiment in space are going to be fully exploited

Twin pregnancy outcome following teriflunomide treatment in a relapsing-remitting multiple sclerosis patient: A case report

Rationale: Teriflunomide is a disease-modifying drug that has been approved for treatment of relapsing-remitting multiple sclerosis. Due to its teratogenic effect in animals, however, it is not recommended during pregnancy. For this reason, effective contraception must be used during its administration. When an unscheduled pregnancy occurs during therapy, patients must undergo a cholestyramine procedure for rapid flushing of the drug. Patient concerns: We describe the case of a 35-year-old female patient suffering diagnosed with relapsing-remitting multiple sclerosis at the age of 20. The patient as a result of side effects of previous therapies started taking teriflunomide. Diagnosis: Despite recommendations for the use of contraceptives, the patient became pregnant during drug therapy. Pregnancy occurred 12 months after initiating teriflunomide treatment. Interventions: Therapy with teriflunomide was immediately suspended and cholestyramine was prescribed (8 g 3 times a day, for 11 days) to flush out any residual drug from the body. Outcomes: Despite an 8-week exposure to teriflumomide during gestation, the patient gave birth to healthy twin girls at 35 week. Controls carried out after birth did not reveal any malformation or genetic and chromosomal abnormality. At a 5-month pediatric specialist check both babies were healthy and growing regularly. Conclusion: This shows that even if there is evidence of teratogenic effects in animals, an 8-week exposure to teraflunomide &gt;0.02 mg/L did not have effects on the newborn

A Movement-Tremors Recorder for Patients of Neurodegenerative Diseases

Neurodegenerative diseases such as Alzheimer, Parkinson, motor neuron, and Chorea affect millions of people today. Their effect on the central nervous system causes the loss of brain functions as well as motor disturbances and sometimes cognitive deficits. In such a scenario, the monitoring and evaluation of early symptoms are mandatory for the improvement of the patient's quality of life. Here, the authors describe the development, the laboratory calibration, and the "in-field validation" under the medical supervision of a movement tremors recorder for subjects affected by neurodegenerative diseases. The developed device is based on an array of four accelerometers connected to an embedded development board. This system is able to monitor tremor/movement, accidental falls, and, moreover, it can track the Alzheimer subjects' geographical position. A remote supervisor can collect data from the system through Bluetooth, Wi-Fi, or GSM connections. A data compression algorithm was developed directly on board in order to increase the efficiency of data transmission and reduce power consumptions