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Abstract Rhizomania is one of the most destructive and damaging sugar beet diseases that has spread in different regions of Iran. In order to evaluate the genotypic, environmental, and genotype by environmental variability of sugar beet genotypes under rhizomania infection, variance components were estimated from the trial series in 7 years. Required data, such as yield and quality parameters, were collected from value for cultivation and use trials. Results of analysis of variance showed that the environment was the source that explained most of the variability, except for amino‐N and alkalinity. Quality traits were also influenced by the environment × cultivar interaction, so that 4.8% (white sugar content) to 46.1% (alkalinity) variance was observed. In contrast, genetic variation was much lower, between 1.2% (potassium) and 27.4% (amino‐N). A strong and negative correlation was found between root yield, sugar yield, and white sugar content with the disease index, which obviously illustrates the negative impact of the rhizomania on root weight and as a consequence on the dependent traits. The cluster analysis of the cultivars based on the quantitative and qualitative traits and the disease index showed that the range of variation in traits, such as the disease index, varied from 6.25 for the susceptible cultivar to 1.25 for the resistant one. This indicates the existence of sufficient genetic diversity among cultivars in terms of this trait. High impurity accumulation was observed in Shiraz region compared with Mashhad. In conclusion, it is observed that rhizomania has a significant effect on the impurity concentration in the root, especially sodium, potassium, and amino‐N. This is very important in the sugar industry because sugar extraction depends on the concentration of these impurities, in addition to the sugar content of each cultivar.

IntroductionThe main aim of the present study was to examine whether the use of a low-tech tool, called click4all, inserted into cognitive and motor training can increase social interaction of patients with Rett Syndrome (RTT) with classmates in a school setting.MethodsTwenty-seven participants with RTT were randomly assigned to two groups: the experimental group received treatment with click4all, and the control group received traditional treatment without click4all. Parameters were measured before treatment (T1), 6 months after treatment (T2), 6 months after the second treatment phase (T3) and at the end of the third treatment phase (T4).ResultsThe results demonstrated an increase in levels of social interaction among classmates and patients with RTT in the experimental group, over time, compared to the control group, 95% CI [5.20–15.30]. Classmates also showed a higher level of knowledge related to participants of the experimental group, and this increased over time, 95% CI [24.98–63.52]. The level of knowledge related to the control group was stable over time and lower than the experimental group.DiscussionThis study demonstrated that the use of a low-tech tool can increase social interactions of patients with RTT in a school setting. This is important, as patients with RTT are often restricted in an isolation condition.

Vascular dementia, the second most common type of dementia, currently lacks a definitive cure. In the pursuit of therapies aimed at slowing its progression and alleviating symptoms, transcranial direct current stimulation (tDCS) emerges as a promising approach, characterized by its non-invasive nature and the ability to promote brain plasticity. In this study, the primary objective was to investigate the effects of a two-week cycle of tDCS on the dorsolateral prefrontal cortex (DLPFC) and neurophysiological functioning in thirty patients diagnosed with vascular dementia. Each participant was assigned to one of two groups: the experimental group, which received anodal tDCS to stimulate DPCFL, and the control group, which received sham tDCS. Neurophysiological functions were assessed before and after tDCS using P300 event-related potentials (ERPs), while neuropsychological function was evaluated through a Mini-Mental State Examination (MMSE). The results showed a reduction in P300 latency, indicating a faster cognitive process; an increase in P300 amplitude, suggesting a stronger neural response to cognitive stimuli; and a significant improvement in MMSE scores compared to the control group, indicating an overall enhancement in cognitive functions. These findings suggest that tDCS could represent a promising therapeutic option for improving both neurophysiological and cognitive aspects in patients with vascular dementia.

La generación de nuevos materiales genéticos para atender las diversas demandas del mercado de la madera requiere una constante evaluación de sus propiedades tecnológicas. En el presente estudio, se evaluó el contenido relativo de duramen y albura a tres alturas de fuste (0,10 m, 2,80 m y 5,50 m) así como la variación de densidad en dirección axial y radial de clones puros Eucalyptus grandis (rose gum) e híbridos (Eucalyptus grandis (rose gum) x Eucalyptus camaldulensis (red gum) y Eucalyptus grandis (rose gum) x Eucalyptus tereticornis (red irongum)) de 11 años de edad. Los clones puros mostraron un 10 % más de duramen que los híbridos. El material híbrido alcanzó el mayor valor medio de densidades, siendo más homogéneo en el perfil radial y axial. En general, la densidad presentó un patrón creciente en la dirección radial. No se encontraron diferencias significativas en la densidad para las alturas estudiadas en los clones híbridos, mientras que los clones puros presentaron valores de densidad significativamente mayores a 0,10 m. La densidad de la albura fue mayor que la del duramen para las tres alturas de fuste en todos los materiales genéticos. El análisis de los resultados indica que los clones híbridos podrían ser aptos para la producción de pulpa de celulosa debido a la menor proporción de duramen, lo cual facilita el proceso de blanqueo, así como para su uso como madera aserrada o contrachapado estructural por su mayor densidad y homogeneidad en altura.

Background: Long-Covid, characterized by persistent symptoms following acute Covid-19 infection, represents a complex challenge for the scientific community. Among the most common and debilitating manifestations, cognitive fog is a neurological disorder characterized by mental confusion and cognitive difficulties. In this study, we investigated the long-term effects of previous Covid-19 infection on cortical brain activity in patients experiencing cognitive fog symptoms in the medium and long term. Methods: A total of 40 subjects (20 females and 20 males) aged between 45 and 70 years (mean age (M) = 59.78, standard deviation (SD) = 12.93) participated in this study. This sample included individuals with symptoms of cognitive fog, both with and without anosmia, and a control group comprised of healthy subjects. All electroencephalography (EEG) data were collected in two sessions, 1 month and 8 months after recovery from Covid-19, to measure the neurophysiological parameters of P300 and beta band rhythms. Results: The results revealed significant differences in the neurophysiological parameters of P300 and beta band rhythms in subjects affected by cognitive fog, and these alterations persist even 8 months after recovery from Covid-19. Interestingly, no significant differences were observed between the participants with anosmia and without anosmia associated with cognitive fog. Conclusions: These findings provide a significant contribution to understanding the long-term effects of Covid-19 on the brain and have important implications for future interventions aimed at managing and treating brain fog symptoms. The longitudinal assessment of cortical brain activity helps highlight the persistent impact of the virus on the neurological health of Long-Covid patients.

Background: Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease with high mortality due to early metastatic dissemination and high chemoresistance. All these factors are favored by its extracellular matrix (ECM)-rich microenvironment, which is also highly hypoxic and acidic. Gemcitabine (GEM) is still the first-line therapy in PDAC. However, it is quickly deaminated to its inactive metabolite. Several GEM prodrugs have emerged to improve its cytotoxicity. Here, we analyzed how the acidic/hypoxic tumor microenvironment (TME) affects the response of PDAC cell death and invadopodia-mediated ECM proteolysis to both GEM and its C18 prodrug. Methods: For this, two PDAC cell lines, PANC-1 and Mia PaCa-2 were adapted to pHe 6.6 or not for 1 month, grown as 3D organotypic cultures and exposed to either GEM or C18 in the presence and absence of acidosis and the hypoxia inducer, deferoxamine. Results: We found that C18 has higher cytotoxic and anti-invadopodia activity than GEM in all culture conditions and especially in acid and hypoxic environments. Conclusions: We propose C18 as a more effective approach to conventional GEM in developing new therapeutic strategies overcoming PDAC chemoresistance.

Parkinson’s disease (PD) is a prevalent neurodegenerative disorder, primarily associated with dopaminergic neuron depletion in the Substantia Nigra. Current treatment focuses on compensating for dopamine (DA) deficiency, but the blood–brain barrier (BBB) poses challenges for effective drug delivery. Using differentiated SH-SY5Y cells, we investigated the co-administration of DA and the antioxidant Grape Seed Extract (GSE) to study the cytobiocompability, the cytoprotection against the neurotoxin Rotenone, and their antioxidant effects. For this purpose, two solid lipid nanoparticle (SLN) formulations, DA-co-GSE-SLNs and GSE-ads-DA-SLNs, were synthesized. Such SLNs showed mean particle sizes in the range of 187–297 nm, zeta potential values in the range of −4.1–−9.7 mV, and DA association efficiencies ranging from 35 to 82%, according to the formulation examined. The results showed that DA/GSE-SLNs did not alter cell viability and had a cytoprotective effect against Rotenone-induced toxicity and oxidative stress. In addition, this study also focused on the evaluation of Alpha-synuclein (aS) levels; SLNs showed the potential to modulate the Rotenone-mediated increase in aS levels. In conclusion, our study investigated the potential of SLNs as a delivery system for addressing PD, also representing a promising approach for enhanced delivery of pharmaceutical and antioxidant molecules across the BBB.

In disorders of consciousness, verticalization is considered an effective type of treatment to improve motor and cognitive recovery. Our purpose is to investigate neurophysiological effects of robotic verticalization training (RVT) in patients with minimally conscious state (MCS). Thirty subjects affected by MCS due to traumatic or vascular brain injury, attending the intensive Neurorehabilitation Unit of the IRCCS Neurolesi (Messina, Italy), were included in this retrospective study. They were equally divided into two groups: the control group (CG) received traditional verticalization with a static bed and the experimental group (EG) received advanced robotic verticalization using the Erigo device. Each patient was evaluated using both clinical scales, including Levels of Cognitive Functioning (LCF) and Functional Independence Measure (FIM), and quantitative EEG pre (T0) and post each treatment (T1). The treatment lasted for eight consecutive weeks, and sessions were held three times a week, in addition to standard neurorehabilitation. In addition to a notable improvement in clinical parameters, such as functional (FIM) (p < 0.01) and cognitive (LCF) (p < 0.01) outcomes, our findings showed a significant modification in alpha and beta bands post-intervention, underscoring the promising effect of the Erigo device to influence neural plasticity and indicating a noteworthy difference between pre-post intervention. This was not observed in the CG. The observed changes in alpha and beta bands underscore the potential of the Erigo device to induce neural plasticity. The device’s custom features and programming, tailored to individual patient needs, may contribute to its unique impact on brain responses.

Genomic prediction relates a set of markers to variability in observed phenotypes of cultivars and allows for the prediction of phenotypes or breeding values of genotypes on unobserved individuals. Most genomic prediction approaches predict breeding values based solely on additive effects. However, the economic value of wheat lines is not only influenced by their additive component but also encompasses a non-additive part (e.g., additive × additive epistasis interaction). In this study, genomic prediction models were implemented in three target populations of environments (TPE) in South Asia. Four models that incorporate genotype × environment interaction (G × E) and genotype × genotype (GG) were tested: Factor Analytic (FA), FA with genomic relationship matrix (FA + G), FA with epistatic relationship matrix (FA + GG), and FA with both genomic and epistatic relationship matrices (FA + G + GG). Results show that the FA + G and FA + G + GG models displayed the best and a similar performance across all tests, leading us to infer that the FA + G model effectively captures certain epistatic effects. The wheat lines tested in sites in different TPE were predicted with different precisions depending on the cross-validation employed. In general, the best prediction accuracy was obtained when some lines were observed in some sites of particular TPEs and the worse genomic prediction was observed when wheat lines were never observed in any site of one TPE.

Pancreatic cancer is a highly lethal disease with a 5-year survival rate of around 11–12%. Surgery, being the treatment of choice, is only possible in 20% of symptomatic patients. The main reason is that when it becomes symptomatic, IT IS the tumor is usually locally advanced and/or has metastasized to distant organs; thus, early diagnosis is infrequent. The lack of specific early symptoms is an important cause of late diagnosis. Unfortunately, diagnostic tumor markers become positive at a late stage, and there is a lack of early-stage markers. Surgical and non-surgical cases are treated with neoadjuvant and/or adjuvant chemotherapy, and the results are usually poor. However, personalized targeted therapy directed against tumor drivers may improve this situation. Until recently, many pancreatic tumor driver genes/proteins were considered untargetable. Chemical and physical characteristics of mutated KRAS are a formidable challenge to overcome. This situation is slowly changing. For the first time, there are candidate drugs that can target the main driver gene of pancreatic cancer: KRAS. Indeed, KRAS inhibition has been clinically achieved in lung cancer and, at the pre-clinical level, in pancreatic cancer as well. This will probably change the very poor outlook for this disease. This paper reviews the genetic characteristics of sporadic and hereditary predisposition to pancreatic cancer and the possibilities of a personalized treatment according to the genetic signature.

Background: Survival rates for metastatic melanoma (MM) patients have improved in recent years, leading to major expenses and health resource use. We conducted a non-concurrent prospective study to describe the burden of hospitalization in a real-world setting for patients with MM. Methods: Patients were tracked throughout all hospital stays in 2004–2019 by means of hospital discharges. The number of hospitalizations, the rehospitalization rate, the average time spent in the hospital and the time span between consecutive admissions were evaluated. Relative survival was also calculated. Results: Overall, 1570 patients were identified at the first stay (56.5% in 2004–2011 and 43.7% in 2012–2019). A total of 8583 admissions were retrieved. The overall rehospitalization rate was 1.78 per patient/year (95%CI = 1.68–1.89); it increased significantly with the period of first stay (1.51, 95%CI = 1.40–1.64 in 2004–2011 and 2.11, 95%CI = 1.94–2.29 thereafter). The median time span between hospitalizations was lower for patients hospitalized after 2011 (16 vs. 26 months). An improvement in survival for males was highlighted. Conclusions: The hospitalization rate of patients with MM was higher in the last years of the study. Compared with a shorter length of stay, patients were admitted to hospitals with a higher frequency. Knowledge of the burden of MM is essential for planning the allocation of healthcare resources.

Abstract Background As a result of the technological progress, the use of sensors for crop survey has substantially increased, generating valuable information for modelling agricultural data. Plant spectroscopy jointly with statistical modeling can potentially help to assess certain chemical components of interest present in plants, which may be laborious and expensive to obtain by direct measurements. In this research, the phosphorus content in wheat grain is modeled using reflectance information measured by a hyperspectral sensor at different wavelengths. A Bayesian procedure for selecting variables was used to identify the set of the most important spectral bands. Additionally, three different models were evaluated: the first model assumes that the observations are independent, the other two models assume that the observations are spatially correlated: one of the proposed models, assumes spatial dependence using a Conditionally Autoregressive Model (CAR), and the other through an exponential correlogram. The goodness of fit of the models was evaluated by means of the Deviance Information Criterion, and the predictive power is evaluated using cross validation. Results We have found that CAR was the model that best fits and predicts the data. Additionally, the selection variable procedure in the CAR model reveals which wavelengths in the range of 500–690 nm are the most important. Comparing the vegetative indices with the CAR model, it was observed that the average correlation of the CAR model exceeded that of the vegetative indices by 23.26%, − 1.2% and 22.78% for the year 2010, 2011 and 2012 respectively; therefore, the use of the proposed methodology outperformed the vegetative indices in prediction. Conclusions The proposal to predict the phosphorus content in wheat grain using Bayesian approach, reflect with the results as a good alternative.

The main aim of the present study was to examine the effects of psychosocial and cognitive stress on executive functions and automatic processes in healthy subjects. To achieve these purposes, we investigated whether cognitive stress impaired the controlled processing underlying cognitive flexibility, working memory and initial letter fluency performances, and whether social stress impaired both performance of executive processes and of semantic fluency. We employed the psychosocial stress paradigm in which cognitive assessment was superimposed on cognitive and social stressors soon after their introduction and was carried out concurrently while they were present. With reference to cognitive stress, we employed the dual-task paradigm that involves a primary task (performances related to executive functions and automatic task) and a secondary task (focusing attention and memorizing items in another cognitive task). Eighty-eight healthy subjects, between 18 and 30 years, participated in this study. They were randomly divided into three groups: two groups undergoing a stress procedure, respectively a cognitive stress group and a social stress group, and a control group. Results indicated that stress impaired cognitive flexibility, working memory and verbal fluency. Cognitive flexibility was affected to a greater extent by psychosocial stress than cognitive stress. This study suggests that the negative effects of stress on cognitive flexibility may be a consequence of the interplay between controlled and automatic processes., Author(s): Rosa Angela Fabio [sup.1] , Giulia Picciotto [sup.1] , Tindara Caprì [sup.1] Author Affiliations: (1) grid.10438.3e, 0000 0001 2178 8421, Department of Clinical and Experimental Medicine, University of Messina, [...]

Objectives: Rare tumors (RT) collectively account for one quarter of all malignancies in Italy. The low frequency and the large heterogeneity in natural history and outcome of individual diseases, together with a scarcity of epidemiological information make them a challenge for clinical practice, as well as for public healthcare organizations. We conducted a retrospective study to quantify the burden of hospitalization in a real-word setting in patients diagnosed with these diseases in an Italian region. Methods: RT patients were tracked along all hospital stays from 2000 to 2019 using hospital discharge records. Frequency of hospitalizations, average time spent in hospital and median timespan between consecutive admissions were considered. Re-hospitalization rates were analyzed through a multivariable negative binomial regression analysis to adjust for confounding and allowing for over-dispersion in count data. Results: As a whole, 57,329 patients were identified at first stay for all studied tumors. A total of 183,959 admissions were retrieved, along a median of 3 hospitalizations per patient. Median timespan between hospitalizations shortened in the course of the study years (12.5 months in 2000–2004 to 5.4 months in 2015–2019). The overall re-hospitalization rate increased from 0.92 per patient/year (95% CI = 0.81–1.04) in 2000–2004 to 2.17 (95% CI = 1.90–2.47) in 2015–2019. Conclusions: Overall, the hospitalization rate of patients with a RT increased in the twenty years since the 2000 and particularly doubled starting from 2015. A higher burden of hospitalizations was found for tumors of the central nervous system, thoracic cavity, digestive tract and sarcomas. To the best of our knowledge this is the first paper related to access to Italian healthcare facilities of patients with these tumors.

This study delves into the intricate relationship among peace attitudes, personality traits, and sustainable behaviors in a diverse sample of 279 adults from different regions of Italy. Building upon the existing literature, this research affirms the influence of agreeableness, openness, and conscientiousness as primary personality traits associated with sustainable behaviors. Additionally, this study scrutinizes the unique predictive power of peace attitudes. The Peace Attitude Scale (PAS), the Big Five Questionnaire (BFQ), and the Sustainable Behaviors Scale (SBS) were utilized to evaluate peace attitudes, personality traits, and sustainable behaviors. The analysis reveals that peace attitudes significantly predict sustainable behaviors, accounting for 31% of the variance. This predictability is attributed to intrinsic motivation and value alignment. Importantly, peace attitudes extend beyond environmental concerns to embrace social justice and equity, integral components of sustainability. The findings underscore the unique and substantial contribution of peace attitudes to understanding sustainable behavior. This study not only confirms the role of personality traits but also emphasizes the importance of intrinsic values in propelling pro-environmental actions.

Background: Parkinson’s disease is one of the most common neurodegenerative disorders. While a definitive cure for Parkinson’s disease remains elusive, a range of treatments are available to slow its progression and counteract its symptoms. Transcranial direct current stimulation (tDCS) represents a non-invasive method to induce brain plasticity. The aim of this study was to examine the effects of two weeks of tDCS on the left dorsolateral prefrontal cortex (DLPFC) on the neurophysiological functioning of Parkinson’s patients. Methods: Thirty patients aged between 67 and 82 years with Parkinson’s disease participated to the experiment. Fifteen underwent tDCS on the left DLPFC, while fifteen underwent sham tDCS. Neurophysiological functions were assessed before and after tDCS using electroencephalogram methods for alpha and beta band rhythms and P300 event-related potential latency. Results: tDCS led to a reduction in the onset latency of the P300 response and an increase in the power spectrum of the alpha and beta band rhythms. Conclusions: This research enhances our understanding of the potential effects of tDCS in the context of Parkinson’s disease treatment, as the reduction in P300 latency and the increase in alpha and beta bands are associated with improvements in cognitive aspects.

Cognitive Rehabilitation (CR) is a therapeutic approach designed to improve cognitive functioning after a brain injury, including stroke. Two major categories of techniques, namely traditional and advanced (including virtual reality—VR), are widely used in CR for patients with various neurological disorders. More objective outcome measures are needed to better investigate cognitive recovery after a stroke. In the last ten years, the application of electroencephalography (EEG) as a non-invasive and portable neuroimaging method has been explored to extract the hallmarks of neuroplasticity induced by VR rehabilitation approaches, particularly within the chronic stroke population. The aim of this study is to investigate the neurophysiological effects of CR conducted in a virtual environment using the VRRS device. Thirty patients with moderate-to-severe ischemic stroke in the chronic phase (at least 6 months after the event), with a mean age of 58.13 (±8.33) for the experimental group and 57.33 (±11.06) for the control group, were enrolled. They were divided into two groups: an experimental group and a control group, receiving neurocognitive stimulation using VR and the same amount of conventional neurorehabilitation, respectively. To study neuroplasticity changes after the training, we focused on the power band spectra of theta, alpha, and beta EEG rhythms in both groups. We observed that when VR technology was employed to amplify the effects of treatments on cognitive recovery, significant EEG-related neural improvements were detected in the primary motor circuit in terms of power spectral density and time-frequency domains. Indeed, EEG analysis suggested that VR resulted in a significant increase in both the alpha band power in the occipital areas and the beta band power in the frontal areas, while no significant variations were observed in the theta band power. Our data suggest the potential effectiveness of a VR-based rehabilitation approach in promoting neuroplastic changes even in the chronic phase of ischemic stroke.

Abstract Background Rett Syndrome (RTT) is a severe, neurodevelopmental disorder mainly caused by mutations in the MECP2 gene, affecting around 1 in 10,000 female births. Severe physical, language, and social impairments impose a wide range of limitations in the quality of life of the patients with RTT. Comorbidities of patients with RTT are varied and cause a lot of pain, but communicating this suffering is difficult for these patients due to their problems, such as apraxia that does not allow them to express pain in a timely manner, and their difficulties with expressive language that also do not permit them to communicate. Two studies, a pilot study and a single case study, investigate the manifestation of pain of patients with RTT and propose a suitable scale to measure it. Aims of this study The first aim was to describe pain situations of RTT by collecting information by parents; the second aim was to test and compare existing questionnaires for non-communicating disorders on pain such as Pain assessment in advanced demenzia (PAINAD), the Critical care pain observation tool (CPOT) and the Non-communicating Children’s Pain Checklist-Revised (NCCPC-R) to assess which of them is best related to the pain behavior of patients with RTT. The third aim was to identify the specific verbal and non-verbal behaviors that characterize pain in girls with Rett syndrome, discriminating them from non-pain behaviors. Method Nineteen participants, eighteen girls with RTT and one girl with RTT with 27 manifestations of pain were video-recorded both in pain and base-line conditions. Two independent observers codified the 90 video-recording (36 and 54) to describe their behavioral characteristics. Results The two studies showed that the most significant pain behaviors expressed by girls with respect to the baseline condition, at the facial level were a wrinkled forehead, wide eyes, grinding, banging teeth, complaining, making sounds, crying and screaming, and the most common manifestations of the body were tremors, forward and backward movement of the torso, tension in the upper limbs, increased movement of the lower limbs and a sprawling movement affecting the whole body. Conclusion The results of the two studies helped to create an easy-to-apply scale that healthcare professionals can use to assess pain in patients with Rett’s syndrome. This scale used PAINAD as its basic structure, with some changes in the items related to the behavior of patients with RTT.

We conducted a systematic review of telerehabilitation (TR) interventions on children and young adults with multiple disabilities (MDs). This review aimed to: (a) examine the effectiveness of telerehabilitation (TR) on adaptive skills that have been targeted for intervention; (b) describe the type of devices used in the intervention procedures; (c) summarize the outcomes; and (d) examine the consumer/professional satisfaction of TR. Eleven studies met inclusion criteria. Results suggested that TR is an effective tool in improving the adaptive skills of children and young adults with MDs. Boh consumers and professionals reported high levels of satisfaction and acceptance of TR services. Trends across different types of devices implemented in TR programs are considered and recommendations are made for future research.

Replication is a fundamental aspect of cancer, and replication is about reproducing all the elements and structures that form a cell. Among them are DNA, RNA, enzymes, and coenzymes. All the DNA is doubled during each S (synthesis) cell cycle phase. This means that six billion nucleic acids must be synthesized in each cycle. Tumor growth, proliferation, and mutations all depend on this synthesis. Cancer cells require a constant supply of nucleotides and other macromolecules. For this reason, they must stimulate de novo nucleotide synthesis to support nucleic acid provision. When deregulated, de novo nucleic acid synthesis is controlled by oncogenes and tumor suppressor genes that enable increased synthesis and cell proliferation. Furthermore, cell duplication must be achieved swiftly (in a few hours) and in the midst of a nutrient-depleted and hypoxic environment. This also means that the enzymes participating in nucleic acid synthesis must work efficiently. pH is a critical factor in enzymatic efficiency and speed. This review will show that the enzymatic machinery working in nucleic acid synthesis requires a pH on the alkaline side in most cases. This coincides with many other pro-tumoral factors, such as the glycolytic phenotype, benefiting from an increased intracellular pH. An increased intracellular pH is a perfect milieu for high de novo nucleic acid production through optimal enzymatic performance.

Rett syndrome (RTT) is a neurodevelopmental disorder marked by profound cognitive, communication, and motor impairments. Despite identified genotype/phenotype connections, the extent of clinical severity varies even among individuals sharing the same genetic mutation. Diverse sociocultural environments, such as the level of inclusivity of the scholar system, the time spent with family, and the intensity of the rehabilitative intervention provided, might influence their development diversely. This study examines the severity of RTT in people in Italy and Israel, countries with distinct contradictory approaches to caring for those with intricate disabilities, across two age groups. Data from 136 Italian and 59 Israeli girls and women with RTT were assessed and divided into two age categories: above and below 12 years. The RARS, a standardized RTT-specific clinical severity tool, was administered. Despite no differences in age and genetic characteristics, the Italian group showed better scores in the RARS motor and disease-related characteristics areas in both age groups. Moreover, the young Italian participants gathered better total RARS scores and emotional and behavioral characteristics area scores. Furthermore, the young group showed significantly less scoliosis, foot problems, and epilepsy than the older group. These findings endorse the inclusion of girls with RTT in the regular schooling system for a limited daily period, investing in high activity levels within the home and community environments, and suggest continuously providing the person with daily occasions of physical activity and socialization.