Qualitative Alterations Research Articles

Objective Assessment of Walking Impairments in Myotonic Dystrophy by Means of a Wearable Technology and a Novel Severity Index

Myotonic dystrophy type 1 (DM1) is a genetic inherited autosomal dominant disease characterized by multisystem involvement, including muscle, heart, brain, eye, and endocrine system. Although several methods are available to evaluate muscle strength, endurance, and dexterity, there are no validated outcome measures aimed at objectively evaluating qualitative and quantitative gait alterations. Advantageously, wearable sensing technology has been successfully adopted in objectifying the assessment of motor disabilities in different medical occurrences, so that here we consider the adoption of such technology specifically for DM1. In particular, we measured motor tasks through inertial measurement units on a cohort of 13 DM1 patients and 11 healthy control counterparts. The motor tasks consisted of 16 meters of walking both at a comfortable speed and fast pace. Measured data consisted of plantar-flexion and dorsi-flexion angles assumed by both ankles, so to objectively evidence the footdrop behavior of the DM1 disease, and to define a novel severity index, termed SI-Norm2, to rate the grade of walking impairments. According to the obtained results, our approach could be useful for a more precise stratification of DM1 patients, providing a new tool for a personalized rehabilitation approach.

Antigen presentation in cancer: insights into tumour immunogenicity and immune evasion.

Immune checkpoint blockade, which blocks inhibitory signals of T cell activation, has shown tremendous success in treating cancer, although success still remains limited to a fraction of patients. To date, clinically effective CD8+ T cell responses appear to target predominantly antigens derived from tumour-specific mutations that accumulate in cancer, also called neoantigens. Tumour antigens are displayed on the surface of cells by class I human leukocyte antigens (HLA-I). To elicit an effective antitumour response, antigen presentation has to be successful at two distinct events: first, cancer antigens have to be taken up by dendritic cells (DCs) and cross-presented for CD8+ T cell priming. Second, the antigens have to be directly presented by the tumour for recognition by primed CD8+ T cells and killing. Tumours exploit multiple escape mechanisms to evade immune recognition at both of these steps. Here, we review the tumour-derived factors modulating DC function, and we summarize evidence of immune evasion by means of quantitative modulation or qualitative alteration of the antigen repertoire presented on tumours. These mechanisms include modulation of antigen expression, HLA-I surface levels, alterations in the antigen processing and presentation machinery in tumour cells. Lastly, as complete abrogation of antigen presentation can lead to natural killer (NK) cell-mediated tumour killing, we also discuss how tumours can harbour antigen presentation defects and still evade NK cell recognition.

O023 / #832: PROGNOSTIC IMPLICATION OF EARLY BRAIN CT SCAN IMAGES IN CHILDREN ADMITTED IN PEDIATRIC INTENSIVE CARE UNIT FOLLOWING CARDIAC ARREST.

Aims & Objectives: Cardiac arrest (CA) is often associated to unfavorable outcome. Early evaluation of brain injury is crucial to define neuroprognosis. Our aim is to develop a severity score based on clearly identifiable features of brain computerized tomography (CT), and, secondly, to combine this score with clinical variables to produce a valuable prognostic tool. Methods: This single-center retrospective study included patients admitted to PICU after CA from 2010 to 2019. All children underwent a standardized post-ROSC protocol including targeted temperature management. Five qualitative neuroradiological variables were obtained from a brain CT scan performed in the first 24 hours after CA: cerebral hemorrhage, qualitative alteration of gray/white matter ratio, sulcal effacement, basilar cistern effacement, cerebellar reversal sign. Each variable was considered according to its correlation with the Pediatric Cerebral Performance Category (PCPC) score to elaborate the Early Brain Injury (EBI) score. Results: 48 children victims of CA were included in the study (median age 4.0 years). 23 patients (47.9%) survived after ROSC and 16 (69.6%) had a favorable clinical outcome (PCPC 1-3). On admission, 33 patients (68.8%) presented an abnormal CT scan. The EBI score showed significant correlation with PCPC score (Spearman’s rho 0.49, p<0.01). The multimodal model containing time to ROSC, EBI score and early lactate levels had extreme specificity and sensibility for predicting poor prognosis (AUC 1.000).Conclusions: EBI score, composed by easy-detectable neuroradiological variables, resulted correlated to outcome and, combined with time to ROSC e early lactate levels, provided an accurate model to early predict prognosis in children with CA.

Gut and Reproductive Tract Microbiota Adaptation during Pregnancy: New Insights for Pregnancy-Related Complications and Therapy.

Pregnancy is characterized by maternal adaptations that are necessary to create a welcoming and hospitable environment for the fetus. Studies have highlighted how the microbiota modulates several networks in humans through complex molecular interactions and how dysbiosis (defined as quantitative and qualitative alterations of the microbiota communities) is related to human pathologies including gynecological diseases. This review analyzed how maternal uterine, vaginal, and gut microbiomes could impact on fetus health during the gestational period. We evaluated the role of a dysbiotic microbiota in preterm birth, chorioamnionitis, gestational diabetes mellitus and pre-eclampsia. For many years it has been hypothesized that newborns were sterile organisms but in the past few years this paradigm has been questioned through the demonstration of the presence of microbes in the placenta and meconium. In the future, we should go deeper into the concept of in utero colonization to better understand the role of microbiota through the phases of pregnancy. Numerous studies in the literature have already showed interesting results regarding the role of microbiota in pregnancy. This evidence gives us the hope that microbiota modulation could be a novel strategy to reduce the morbidity and mortality related to pregnancy complications in the future.

Aging-related alteration of trigeminal ganglion structures; A histologic study of Neuronal population, Satellite Ganglionic Cells and Vascular bed

Background: Aging is associated with signs that are similar to peripheral neuropathy and age-related decline in the peripheral sensory system and proprioceptive functions. Trigeminal ganglion (TG) is one of the sensory ganglion providing sensory information from the orofacial region. Ultrastruchral alteration in neuronal population of TG has been reported.Aim of work: Examine the effects of aging on neuronal population, distribution, and satellite ganglionic cells (SGCs) and compare with the TG of young animal. Materials and Methods: Old male Wistar rats (32 weeks old) (250±20g) and young male (4weeks old) (150±20g) were deeply anesthetized with chloroform. To avoid inadvertent mechanical dark neuron formation, each animal was transcardially perfused with 500ml of 4% paraformaldehyde in0.1 M phosphate-buffered saline. The skull cap was cut open and the TG was exposed and removed carefully. The sections were selected according to the systematic random sampling(SRS) and stained with H&E. From each section 10 fields(200×160µm) were selected randomly and the profile of neurons, neuronal shapes, SGCs, and the number of capillary profiles were studied. Results: The measured profile of neurons in the TG of young (17.11± 4.8) and old animals (15.69±4.4) showed a meaningful level of differences(p 0.05). The number of capillary profiles in the TG of young animals (7±2.73) showed a meaningful difference with those of old animals (3.8±0.83) (p < 0.05). Conclusion: With aging neuro-glial population and vascular bed of TG undergo a series of quantitative and qualitative alterations. Precisely aging is associated with decrease in neuronal size and vascular bed while the number of SGCs remains without significant changes. Aging leads to changes in neuronal distribution and likely morphologic alterations in SGCs subpopulation.

Differential Mitochondrial Gene Expression in Adipose Tissue Following Weight Loss Induced by Diet or Bariatric Surgery.

ContextMitochondria are essential for cellular energy homeostasis, yet their role in subcutaneous adipose tissue (SAT) during different types of weight-loss interventions remains unknown.ObjectiveTo investigate how SAT mitochondria change following diet-induced and bariatric surgery–induced weight-loss interventions in 4 independent weight-loss studies.MethodsThe DiOGenes study is a European multicenter dietary intervention with an 8-week low caloric diet (LCD; 800 kcal/d; n = 261) and 6-month weight-maintenance (n = 121) period. The Kuopio Obesity Surgery study (KOBS) is a Roux-en-Y gastric bypass (RYGB) surgery study (n = 172) with a 1-year follow-up. We associated weight-loss percentage with global and 2210 mitochondria-related RNA transcripts in linear regression analysis adjusted for age and sex. We repeated these analyses in 2 studies. The Finnish CRYO study has a 6-week LCD (800-1000 kcal/d; n = 19) and a 10.5-month follow-up. The Swedish DEOSH study is a RYGB surgery study with a 2-year (n = 49) and 5-year (n = 37) follow-up.ResultsDiet-induced weight loss led to a significant transcriptional downregulation of oxidative phosphorylation (DiOGenes; ingenuity pathway analysis [IPA] z-scores: −8.7 following LCD, −4.4 following weight maintenance; CRYO: IPA z-score: −5.6, all P < 0.001), while upregulation followed surgery-induced weight loss (KOBS: IPA z-score: 1.8, P < 0.001; in DEOSH: IPA z-scores: 4.0 following 2 years, 0.0 following 5 years). We confirmed an upregulated oxidative phosphorylation at the proteomics level following surgery (IPA z-score: 3.2, P < 0.001).ConclusionsDifferentially regulated SAT mitochondria-related gene expressions suggest qualitative alterations between weight-loss interventions, providing insights into the potential molecular mechanistic targets for weight-loss success.

Recurring paroxysmal positional vertigo: evaluation of the vascular factor.

SUMMARYTo evaluate the effective incidence of vascular factor in the recurrence of benign paroxysmal positional vertigo (BPPV), we studied 50 subjects, 32 affected by idiopathic recurrent BPPV (study group) and 18 healthy subjects (control group). All subjects underwent complete otoneurological balance and haemodynamic evaluation by extracranial colour-coded duplex sonography (ECCS) of vertebral arteries (VA) with indication of arterial flow in ml/min, and retinal fluorangiography (FAG). The ECCS of 19 patients (59.3%) within the study group presented a reduction in vertebral arterial flow, exceeding the limits established by normative values (< 100 ml/min). In all cases, the same side was affected by BPPV, emphasised by vertebral hypoperfusion. The remaining 13 patients (40.6%) showed an arterial vertebral flow entirely within the normative values. The FAG excluded qualitative alterations of the cerebral microcirculation. The ECCS demonstrated that 59.3% of the study group showed a significant reduction in vertebral arterial flow ipsilateral to the semicircular canal affected by BPPV. This increased to 68.75% when the flow difference (D) between both the vertebral arteries were considered and reached 71.8% when vascular risk factors were evaluated. We conclude that reduced perfusion of the vestibular structures makes an already critical situation even more difficult, which can eventually develop into labyrinth suffering. The absence of fluorangiographic signs suggests that the labyrinthine neuroepithelium is much more sensitive to hypoperfusion than the retina. We hypothesise that this ischaemic situation could degenerate utricular macula, otolith detachment, leading to the development of recurrent BPPV. This risk situation for the labyrinth can also be revealed by the evaluation of three parameters: presence of vascular risk factors, reduction of vertebral flow < 100 ml/min and the difference in flow between the 2 vertebral arteries > 29 ml/min.

A Cross Sectional Study on T Cells and Subsets in Chronic Lymphocytic Leukemia and their Association with Clinical Phenotype.

T cells in B chronic lymphocytic leukaemia (CLL) have been reported to show qualitative and quantitative alterations, thereby regulating the antitumor immune response. We evaluated the absolute count, percentages of T cells and subsets and their association with disease parameters in Indian patients. 45 treatment naïve CLL cases and 10 healthy controls were evaluated for CD3 + Tcells, CD4 + T cells, CD8 + T cells percentage by flowcytometry. The absolute counts were obtained by multiplication with absolute lymphocyte counts obtained on cell counter. The clinical characteristics (age, sex, Rai stage, B symptoms, CD38 expression) were analysed for any association with alteration of these cells (percentages, absolute counts, ratio with monoclonal B cell count) and CD4: CD8 ratio. The mean absolute count of CD3 + T cell, CD4 + T cell and CD8 + T cells was significantly higher (p < 0.05) in CLL patients as compared to healthy controls. CD4:CD8 ratio was variable (normal, increased and decreased). The mean CD8 + T cells count was higher in advanced disease stage, and CD38 positive cases (p > 0.05). Younger CLL patients (< 55years) had greater increase in CD8 + T cells (p > 0.05). Significant alterations in T cells and their subsets were observed in CLL. A trend towards advanced stage, CD38 expression, presentation an early age was seen with increase in CD8 + T cell counts.

Qualitative and Quantitative Ovarian and Peripheral Blood Mitochondrial DNA (mtDNA) Alterations: Mechanisms and Implications for Female Fertility.

The reduction of female fertility over time is considered as a natural consequence of ovarian aging. The exact mechanism underlying this process is not fully elucidated. However, it is becoming increasingly evident that qualitative and quantitative mitochondrial genome alterations might play a relevant role. The former include mitochondrial DNA (mtDNA) damage caused by oxidative stress, the accumulation of acquired mtDNA mutations, the effects of inherited mtDNA mutations, and alterations in the mitochondrial stress response mechanism. The latter refer to alterations in the oocytes, granuolosa cells, and embryonic cells mtDNA content. The present review aims to investigate the evidence about: (1) the effect of qualitative and quantitative mtDNA alterations on female fertility, paying particular attention to those with a pathophysiology characterized by a relevant role of oxidative stress; (2) the use of oocytes, granulosa cells (GCs), embryonic cells, and peripheral blood cells mtDNA copy number as a female fertility surrogate biomarker; (3) experimental therapies tested to try to subvert the ovarian aging process with particular reference to antioxidant treatments.

A Sensitivity and Specificity Diagnosis of Pews is Used to Indicate the Necessity for Hospital Admission and to Predict Serious Disease Among Children

Aim: The advance warning score (Seats), which is legitimized in the crisis department, is less accepted for the prevention of early weakening of a hospitalized teenager. The affectivity and information activity of two PEWSs, usually used in hospital admissions and the first serious disease, were expected to be evaluated. Methods: Required data was disclaimed for patients. Our current research was conducted at Mayo Hospital, Lahore from May 2020 to April 2021. Clinical and rigorous analyses have been performed. We have applied guidelines and usual understanding amongst three intense careers to identify assessments as crucial where not available. Results: 1940 patients have been shattered. 213 confirmations were received (12 percent). There were 1640 clinical (87%) and 277 (15%) cautious therapies. Relatively performing Brighton and COAST Seats. Emergency Clinic Verification-PEWS so 4 (94 INTRODUCTION Since the Brighton Score approval in 20051, other children's early warning scores have been utilized to detect the early deterioration of the infant in hospital. Together with the Pakistan Maternal and Childhood Report, 'Why children bite dust,' the Pakistan National Patient Safety Agency and the Public Hospital and Care Excellence Institute suggested early detection levels to assist children with the beginnings of the underlying illness in the clinic (Considine J, et al, 2019). Although their unlimited performance, the qualitative alterations thought proper, making approval varied for various scores. Introducing an urgent concentration of 4 hours in Pakistan. In order to achieve the continued management decision, a 5-hour emphasis in Pakistan emergency departments is introduced (Pinto C, et al., 2018). 6 Seats using the Brighton- and COAST systems generally employed have been constructed so that trends in the physiological condition of the patient may be reflected and the decay process identified early and the hospitalized kid can thus be quickly identified. In any case, in order to avoid the needs of a health clinic for confirmation, or the severity of the disease, the validity of pre-vising the physiological boundaries in the emergency department is not recognized (Burrell AR, et al., 2016). As the usage of PEWS in emergency services rises, the predictive capacity of this instrument must be known to forecast emergency confirmation and a substantial indicant disease. There are just two explicit studies PEWS capability to predict admission in emergency department percent) was clean, though unnoticeable (34 percent). The area below the AUC was low at 0.693. The AUC is low. Major allegation: PEWS was 95 percent very clear, nevertheless, not sensitive enough in clinical diseases (45 percent). The AUC was 0.756 per person for Brighton and COAST PEWS. The two scores were unsuccessful in predicting critical careful nausea (AUC 0.644). Seats=4 have been successful in predicting major respiratory diseases-76%, 92% specified affectivity. Conclusion: Brighton and Coast Pews both had good results. A score of the fourth is quite certain Therefore, unprotected effectiveness for clinical confirmation and important disease prediction. A high PEWS, however, is a poor prerequisite for confirmation of actual sickness.

Role of high-density lipoprotein cholesterol in health and diseases

Primary function of high-density lipoprotein cholesterol is to reverse transport the cholesterol from extrahepatic cell to liver for its metabolism and excretion. Studies have demonstrated the anti-inflammatory, anti-atherogenic, anti-oxidant, and anti-diabetic property of the high-density lipoprotein cholesterol. Although the exact mechanism still remains unelucidated, high-density lipoprotein cholesterol is a complex of lipids and proteins carrying many associated cargo molecules such as enzymes, signaling molecules, miRNA, which imparts overall functionality of high-density lipoprotein cholesterol for its beneficial health effects. However, the protein and lipids components get transform by the enzymes associated with high-density lipoprotein cholesterol, hyperglycemia, oxidative stressor, and free radicals, leading to qualitative and quantitative alterations in high-density lipoprotein cholesterol (HDLc) and diminishes its beneficial effects. In this review, we have discussed the different property of high-density lipoprotein cholesterol, its function and factors influencing HDLc property in light of anti-inflammatory activity in rheumatoid arthritis and the role of cholesterol-lowering statin drug in enhancing the beneficial effect of high-density lipoprotein cholesterol in different cell types.

FORMS OF MANIFESTATION OF INTERPERSONAL IDENTITY CONFLICTS WITH DIFFERENT CONTROL LOCUS IN CERTAIN AGE PERIODS

The article is devoted to the investigation of the forms of manifestation of interpersonal identity conflicts with different control locus in certain age periods. Forms of manifestation and their solving methods in adolescence and preadult age are different. It is a period of physiological and mental development in adolescence, it characterized by puberty crisis, which refers to the person's qualitative alteration of the general development. Personality of boys and girls is characterized by pubescence, when increased irritation is changing by emotional self-control, they consciously build their communication ways, continue improvement of significant qualities. At that time, increasing tenseness in society, forming a person's worldview, its new social status leads to conflicts,their solution is due to the choosing ability of the right style of behavior in a conflict situation, to analyze the other people style and adapt to a new social environment. A person as a social individual, embodies the most significant social qualities, which determine behavior. A persistent feature, which is forming in the socialization process, is the control locus that allows to explain responsibility for the action's results in different ways. The investigation's attention is focused on such styles of behavior in manifestation conflicts as: rivalry, compromise, adaptation, collaboration, avoidance. According to the results of the investigation, it was determined that the compromise style is more pronounced in preadult age and the preoccupation style is adolescent. There was no statistically significant interconnection between the locus control and conflict behavioral styles. Distinctions of behavior style in the conflict in adolescence and preadult age, which are not due to personal characteristics, were identified. The investigation results would be taken into account in the pedagogical process of secondary schools and in teaching disciplines in higher education institutions.

The COVID-19 pandemic masks the way people perceive faces

The unprecedented efforts to minimize the effects of the COVID-19 pandemic introduce a new arena for human face recognition in which faces are partially occluded with masks. Here, we tested the extent to which face masks change the way faces are perceived. To this end, we evaluated face processing abilities for masked and unmasked faces in a large online sample of adult observers (n = 496) using an adapted version of the Cambridge Face Memory Test, a validated measure of face perception abilities in humans. As expected, a substantial decrease in performance was found for masked faces. Importantly, the inclusion of masks also led to a qualitative change in the way masked faces are perceived. In particular, holistic processing, the hallmark of face perception, was disrupted for faces with masks, as suggested by a reduced inversion effect. Similar changes were found whether masks were included during the study or the test phases of the experiment. Together, we provide novel evidence for quantitative and qualitative alterations in the processing of masked faces that could have significant effects on daily activities and social interactions.

The detrimental qualitative and quantitative alterations of circulating endothelial progenitor cells in patients with bronchiectasis

BackgroundBronchiectasis is an independent risk factor for cardiovascular disease（CVD）and cardiac dysfunction. Endothelial progenitor cells (EPCs) play a crucial role in maintaining endothelial function, and is inversely correlated with cardiovascular risk factors or cardiac dysfunction. However, the relationship between EPCs and bronchiectasis is unknown. MethodsTwenty-nine patients with stable bronchiectasis and 15 healthy controls were recruited. Fasting venous blood were collected for determining circulating EPC number and activity as well as systemic inflammatory cytokines. ResultsThe number and migratory or proliferative activity of circulating EPCs in bronchiectasis patients were significantly reduced (p < 0.001). In high E-FACED group, the number of circulating EPCs evaluated by cell culture assay and EPC proliferation were decreased (p < 0.05). Similarly, the number and function of circulating EPCs were both reduced in low forced expiratory volume in 1 s (FEV1) or high mMRC group (p < 0.05). There was a significant correlation between circulating EPCs and bronchiectasis disease severity, according to the E-FACED score (p < 0.05), particularly to FEV1 (p < 0.05) and mMRC dyspnea score (p < 0.05). The count and activity of EPCs inversely correlated with hsCRP levels and IL-6 levels (p < 0.01). ConclusionsDeficiencies in the number and function of circulating EPCs are present in patients with bronchiectasis. The changes are related to disease severity and may be partly attributed to systemic inflammation. The current findings may provide novel surrogate evaluation biomarkers and potential therapeutic target for bronchiectasis.

Qualitative mucin disorders in patients with primary Sjögren's syndrome: a literature review.

Background It is a common opinion that Primary Sjögren Syndrome (pSS) damages the exocrine glands and determines the reduction of secreted saliva, some studies show that there are qualitative anomalies of the mucins produced in saliva, including MUC7, MUC5B, MUC1. The purpose of this study is to trace all the information useful to establish whether there is a qualitative or quantitative defect of the mucins in the pSS. Material and Methods We reviewed the literature by looking for publications relevant to the topic in electronic databases. Sixteen articles met the search criteria. The studies were divided into two categories, those that studied the rheological characteristics of the saliva and those that studied the structural and / or metabolism modifications of the muciparous cells in the salivary glands. Results in Patients with pSS, xerostomia and the reduction of salivary spinnbarkeit are only partially related to the reduction of the unstimulated salivary flow. In pSS, pathological alterations of mucins’ chemical-physical properties prevail as a cause of the clinical characteristics. Moreover, in pSS there are structural and metabolism changes in salivary glands’ muciparous cells. Conclusions There is much evidence that supports the presence of qualitative alterations in the saliva’s rheological properties in Patients with pSS, and these are the main cause, more than the reduction of the unstimulated salivary flow, of the disease clinical characteristics - dry mouth and complications in the oral cavity. Therefore we propose to add to the classification criteria of pSS also a qualitative test of salivary glycoproteins. Key words:Primary Sjögren's syndrome, mucin, MUC7, MUC5B, MUC1, sulphate oligosaccharides.

Branched Ubiquitination: Detection Methods, Biological Functions and Chemical Synthesis.

Ubiquitination is a versatile posttranslational modification that elicits signaling roles to impact on various cellular processes and disease states. The versatility is a result of the complexity of ubiquitin conjugates, ranging from a single ubiquitin monomer to polymers with different length and linkage types. Recent studies have revealed the abundant existence of branched ubiquitin chains in which one ubiquitin molecule is connected to two or more ubiquitin moieties in the same ubiquitin polymer. Compared to the homotypic ubiquitin chain, the branched chain is recognized or processed differently by readers and erasers of the ubiquitin system, respectively, resulting in a qualitative or quantitative alteration of the functional output. Furthermore, certain types of branched ubiquitination are induced by cellular stresses, implicating their important physiological role in stress adaption. In addition, the current chemical methodologies of solid phase peptide synthesis and expanding genetic code approach have been developed to synthesize different architectures of branched ubiquitin chains. The synthesized branched ubiquitin chains have shown their significance in understanding the topologies and binding partners of the branched chains. Here, we discuss the recent progresses on the detection, functional characterization and synthesis of branched ubiquitin chains as well as the future perspectives of this emerging field.

Application of atomic force microscopy to assess erythrocytes morphology in early stages of diabetes. A pilot study

The study aim was to assess the application of atomic force microscopy (AFM) to evaluate erythrocyte morphology in early stages of type 2 diabetes mellitus, and the association with biochemical, anthropometric, diet, and physical activity indicators.This was a pilot cross-sectional study with four groups: healthy individuals, people with prediabetes (PDG), metabolic syndrome (MSG), and diabetes mellitus group (DMG). Blood samples were obtained to assess the erythrocyte morphology and biochemical parameters. Anthropometrical measurements were taken. Besides, a diet and a physical activity questionnaire were applied.The evaluation of the erythrocyte morphology through the AFM showed quantitative and qualitative alterations in the cell's form and size. Compared to the healthy group, the PDG had a reduction in height (-0.80 μm, p < 0.05), and an increase in axial ratio (-0.09 μm, p < 0.05); the MSG had lower concave depth (-0.19 μm, p < 0.05); and the DMG had a decreased height (-0.46 μm, p < 0.05) and concave depth (-0.29 μm, p < 0.05), and higher axial ratio (+0.08 μm) and thickness (+0.32 μm, p < 0.05). The PDG vs. DMG had a statistically significant difference in concave depth (+0.23 μm, p < 0.05) and thickness (-0.26 μm, p < 0.05). The MSG was different than the DMG in variables like axial ratio (-0.05 μm) and thickness (-0.25 μm). Besides, higher values of age, HbA1c, triglycerides, body mass index, waist-to-hip ratio, and physical inactivity were associated with altered erythrocyte morphology.AFM is a promising instrument to assess early but subtle changes in erythrocyte morphology (height, axial ratio, concave depth, thickness) before significant pathological conditions, such as type 2 diabetes mellitus. HbA1c might have a major effect in altered morphology, vs. metabolic parameters like high triglycerides, body mass index, waist, and physical inactivity.

Rejuvenated Circulating Endothelial Progenitor Cells and Nitric Oxide in Premenopausal Women with Hyperhomocysteinemia

Hyperhomocysteinemia (HHcy) induced endothelial dysfunction is associated with disturbance in circulating endothelial progenitor cells (EPCs). Nevertheless, whether this unfavorable effect of HHcy on circulating EPCs also exists in premenopausal women is still unknown. Therefore, this leaves an area for the investigation of the difference on the number and activity of circulating EPCs in premenopausal women with hyperhomocysteinemia and its underlying mechanism. The number of circulating EPCs was measured by fluorescence-activated cell sorter analysis, as well as DiI-acLDL and lectin fluorescent staining. The migration and proliferation of circulating were evaluated by the Transwell chamber assay and MTT. Additionally, the endothelial function and levels of nitric oxide (NO), VEGF, and GM-CSF in plasma and culture medium were determined. The number or activity of circulating EPCs and flow-mediated dilatation (FMD) in premenopausal women with or without HHcy were higher than those in postmenopausal women. However, no significant effect of HHcy on the number or activity of circulating EPCs in premenopausal women was observed. A similar alteration in NO level between the four groups was observed. There was a correlation between FMD and the number or activity of EPCs, as well as NO level in plasma or secretion by EPCs. For the first time, our findings illuminated the quantitive or qualitative alterations of circulating EPCs and endothelial function in premenopausal patients with HHcy are preserved, which was associated with retained NO production. The recuperated endothelial repair capacity is possibly the potential mechanism interpreting cardiovascular protection in premenopausal women with HHcy.

Quantitative and qualitative alterations of circulating myeloid cells and plasmacytoid DC in SARS-CoV-2 infection.

SARS-CoV-2 is responsible for a new infectious disease (COVID-19) in which individuals can either remain asymptomatic or progress from mild to severe clinical conditions including acute respiratory distress syndrome and multiple organ failure. The immune mechanisms that potentially orchestrate the pathology in SARS-CoV-2 infection are complex and only partially understood. There is still paucity of data on the features of myeloid cells involved in this viral infection. For this reason, we investigated the different activation status profiles and the subset distribution of myeloid cells and their correlation with disease progression in 40 COVID-19 patients at different stages of disease. COVID-19 patients showed a decrease in the absolute number of plasmacytoid and myeloid dendritic cells, different subset distribution of monocytes and different activation patterns of both monocytes and neutrophils, coupled to a significant reduction of HLA-DR monocyte levels. We found that some of these alterations are typical of all COVID-19 patients, while some others vary at different stages of the disease and correlate with biochemical parameters of inflammation. Collectively, these data suggest that not only the lymphoid, but also the myeloid compartment, is severely affected by SARS-CoV-2 infection.

Neurofibromatosis Type 1: Ocular Electrophysiological and Perimetric Anomalies.

IntroductionNeurofibromatosis type 1 (NF1) is a multisystemic disease caused by the mutation of Nf1 gene located on chromosome 17q11.2. The mutation determines the loss of function of the protein neurofibromin with consequent uncontrolled cellular proliferation. Patients are characterized by a wide range of dermatological, neurological, and ophthalmological symptoms.PurposeThe aim of the study was to evaluate, through pattern visual evoked potentials (p-VEPs) and frequency doubling technology (FDT) Matrix perimetry, the objective and psychophysical functionality of the optic pathways in a group of NF1 patient.MethodsThe study group consisted of 26 patients affected by NF1 and 17 healthy controls. Each patient underwent a complete ophthalmological examination, p-VEPs with the evaluation of amplitude and latency of the P100 wave, and FDT perimetry, with the evaluation of central sensitivity (CS), mean deviation (MD), pattern standard deviation (PSD) and glaucoma hemifield test (GHT).ResultsNF1 patients showed a statistically significant alteration in the transmission of visual impulse. P-VEPs results highlighted a reduced amplitude and an increased latency of the P100 wave, suggesting an involvement of the visual pathway. Visual field analysis showed a significant reduction in all the observed parameters as well (CS, MD, PSD, and GHT).ConclusionThe present study showed, in NF1 patients, a qualitative and quantitative alteration in the conduction of stimuli through the visual pathways. The observed alterations are present, although, only at a subclinical level. None of the patients included in the study showed any manifest visual deficit nor had any concomitant pathology that might have affected the outcome of the study. In conclusion, electrophysiological exams and computer perimetry may take part, alongside a wider array of exams, in the differential diagnosis and later monitoring of NF1.