Spike mutation resilient scFv76 antibody counteracts SARS-CoV-2 lung damage upon aerosol delivery.

The uneven worldwide vaccination coverage against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and emergence of variants escaping immunity call for broadly effective and easily deployable therapeutic agents. We have previously described the human single-chain scFv76 antibody, which recognizes SARS-CoV-2 Alpha, Beta, Gamma and Delta variants. We now show that scFv76 also neutralizes the infectivity and fusogenic activity of the Omicron BA.1 and BA.2 variants. Cryoelectron microscopy (cryo-EM) analysis reveals that scFv76 binds to a well-conserved SARS-CoV-2 spike epitope, providing the structural basis for its broad-spectrum activity. We demonstrate that nebulized scFv76 has therapeutic efficacy in a severe hACE2 transgenic mouse model of coronavirus disease 2019 (COVID-19) pneumonia, as shown by body weight and pulmonary viral load data. Counteraction of infection correlates with inhibition of lung inflammation, as observed by histopathology and expression of inflammatory cytokines and chemokines. Biomarkers of pulmonary endothelial damage were also significantly reduced in scFv76-treated mice. The results support use of nebulized scFv76 for COVID-19 induced by any SARS-CoV-2 variants that have emerged so far.

Human inhalable antibody fragments neutralizing SARS-CoV-2 variants for COVID-19 therapy.

As of December 2021, coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains a global emergency, and novel therapeutics are urgently needed. Here we describe human single-chain variable fragment (scFv) antibodies (76clAbs) that block an epitope of the SARS-CoV-2 spike protein essential for ACE2-mediated entry into cells. 76clAbs neutralize the Delta variant and other variants being monitored (VBMs) and inhibit spike-mediated pulmonary cell-cell fusion, a critical feature of COVID-19 pathology. In two independent animal models, intranasal administration counteracted the infection. Because of their high efficiency, remarkable stability, resilience to nebulization, and low cost of production, 76clAbs may become a relevant tool for rapid, self-administrable early intervention in SARS-CoV-2-infected subjects independently of their immune status.

Evaluating best evidence in occupational therapy for patients with hip replacement: guidelines.

SUMMARY: Object. The following study was carried out in order to evaluate through guidelines the best evidence in occupational therapy for daily activities and quality of life of patients with hip prostheses. Methods. Recommendations were generated following the grading method of the National Program for Guidelines/National System Guidelines (PNLG-SNLG), a system for developing guidelines for recommendations in clinical practice. The Appraisal of Guidelines Research and Evaluation in Europe (AGREE) tool was also applied. Results. A total of seven studies were included in this research: one randomized controlled trial, two systematic reviews, two outcomes research studies, and two observational studies. We found that, for the three clinical questions we proposed, more research on the effectiveness of treatments is required. Conclusions. The evidence resulting from this study is not sufficient to determine whether the rehabilitation techniques under consideration are effective.

Delayed presentation of children to the emergency department during the first wave of COVID-19 pandemic in Italy: Area-based cohort study.

AIM: To ascertain a delay in attendances to the emergency department (ED) during 2020 lockdown. METHODS: Area-based cohort study on paediatric (0-15 years) attendances resulting in hospital admission in Tuscany, Italy, in February-May 2020, and the corresponding periods in 2018-19. We analysed times from symptom onset to arrival, the odds of arriving late (>90th centile of time) and paediatricians' judgements of a late presentation by logistic models. RESULTS: As expected, ED attendance fell sharply (-62%) in 2020 vs 2018-19. As for cases studied (455 in 2020 and 1161 in 2018-19), we documented a delay in arrival to the ED in 2020 versus 2018-19 for several groups of diagnoses, namely gastroenteritis, sepsis, wounds, burns and infections overall. Time to presentation over 90th centile was also higher in 2020 (odds ratio, OR: 1.44; 95% confidence interval: 1.00, 2.06), as were paediatricians' judgements of a late arrival (18.9% of cases in 2020 vs. 13.4% in 2018-19; OR: 1.58; 1.14, 2.19) CONCLUSION: In a population-based cohort, delayed attendances to ED ascertained both subjectively and objectively convey the message to families and to paediatricians to seek hospital care in case of severe or unremitting symptoms and not to wait longer than they normally would.

Evaluation of the Psychometric Properties of the Scale A-ONE: An Italian Cross-Sectional Study.

PURPOSE: This study is aimed at validating the A-ONE scale in an Italian population with Central Nervous System (CNS) dysfunction. Material and Methods. Between May and November 2018, people aged between 60 and 90 with CNS dysfunction were recruited in a hospital in Rome, Italy. Patients were observed and evaluated during the activities of daily living. Internal consistency and reliability were evaluated with Cronbach's coefficient alpha and intraclass correlation coefficient, respectively. As measured with Pearson's correlation coefficient, the validity was examined comparing results of the A-ONE with the Barthel index. Responsiveness was evaluated 30 days after the first administration. RESULTS: A total of 70 people having a diagnosis of neurological disorders were evaluated. The internal consistency showed Cronbach's coefficient alpha ranging from 0.634 to 0.959. The measurement of reliability varied from 0.984 to 0.997 for intrarater and from 0.979 to 0.998 for interrater. Pearson's correlation coefficient between the A-ONE and the Barthel index and the responsiveness showed statistically significant values (p < 0.01). CONCLUSIONS: The present study provides preliminary evidence of reliability, validity, and responsiveness of the A-ONE when using elderly people with CNS dysfunction.

Antibody drug conjugates with hydroxamic acid cargos for histone deacetylase (HDAC) inhibition.

Antitumor hydroxamates SAHA and Dacinostat have been linked to cetuximab and trastuzumab through a non-cleavable linker based on the p-mercaptobenzyl alcohol structure. These antibody drug conjugates (ADCs) were able to inhibit HDAC in several tumour cell lines. The cetuximab based ADCs block human lung adenocarcinoma cell proliferation, demonstrating that bioconjugation with antibodies is a suitable approach for targeted therapy based on hydroxamic acid-containing drugs. This work also shows that ADC-based delivery might be used to overcome the classical pharmacokinetic problems of hydroxamic acids.

Ten Years of Pediatric Lung Ultrasound: A Narrative Review.

Lung diseases are the most common conditions in newborns, infants, and children and are also the primary cause of death in children younger than 5 years old. Traditionally, the lung was not thought to be a target for an ultrasound due to its inability to penetrate the gas-filled anatomical structures. With the deepening of knowledge on ultrasound in recent years, it is now known that the affected lung produces ultrasound artifacts resulting from the abnormal tissue/gas/tissue interface when ultrasound sound waves penetrate lung tissue. Over the years, the application of lung ultrasound (LUS) has changed and its main indications in the pediatric population have expanded. This review analyzed the studies on lung ultrasound in pediatrics, published from 2010 to 2020, with the aim of highlighting the usefulness of LUS in pediatrics. It also described the normal and abnormal appearances of the pediatric lung on ultrasound as well as the benefits, limitations, and possible future challenges of this modality.

Chest Computed Tomography and Lung Ultrasound Findings in COVID-19 Pneumonia: A Pocket Review for Non-radiologists.

COVID-19 is an infectious disease that has quickly spread worldwide, causing a pandemic. The main clinical manifestation is pneumonia. The most important test for the diagnosis is represented by RT-PCR, but, given the limited sensitivity, further radiological examinations are necessary. We reviewed the literature to highlight the typical manifestations and advantages of chest computed tomography and lung ultrasound in COVID-19 pneumonia in order to assist clinical researchers in the management of this disease.

The clinical course of SARS-CoV-2 positive neonates.

The COVID-19 pneumonia was firstly reported in Wuhan, China, in December 2019. The disease had a rapid spread all over the word becoming an international public health emergency. Limited data were available on COVID-19 positive neonates. We reviewed relevant literature to understand the clinical course of disease and transmission routes in affected neonates. The aim of the study was evaluating the clinical course and prognosis of SARS-CoV-2 positive neonates. Based on current literature, the hypothesis of vertical transmission of SARS-CoV-2, though conceivable, remains unproven. A research conducted on PubMed database from December 2019 to April 27, 2020 revealed that were reported 25 neonates affected by SARS-CoV-2. Main symptoms were fever, cough, or shortness of breath but often these neonates did not show other symptoms during length stay in hospital. No deaths occurred.

A randomized controlled study of immediate versus delayed umbilical cord clamping in infants born by elective caesarean section.

BACKGROUND: Delayed umbilical cord clamping is associated with greater haemoglobin concentration and iron storage between 3 and 6 months of life and with less need of blood transfusion and lower incidence of neonatal hypotension compared to early umbilical cord clamping. METHODS: The aim was to test the hypothesis that delayed cord clamping is better than early cord clamping in term infants born by elective caesarean section. Group A was subjected to immediate cord clamping while in the Group B, the umbilical cord was clamped 1 min after birth. Primary aim was revealed the difference in pre-ductal saturation between two groups while secondary aim was investigating the difference in HR, Ht, bilirubin and glycaemia. Pre-ductal SpO2 and HR were recorded at 5 and 10 min after birth, T was analysed 10 min after birth, glycaemia was revealed at 120 min while Ht and bilirubin were collected at 72 h. RESULTS: 132 newborns were enrolled in the study and allocated in ratio 1:1 to group A or B. Delayed cord clamping did not improve SpO2, HR and T values compared to immediate cord clamping (p > 0,05). However, Group B showed greater haematocrit and bilirubin values at 72 h compared to Group A (56,71 ± 6663 vs 51,56 ± 6929; p < 0,05 and 8,54 ± 2,90 vs 7,06 ± 2,76; p < 0,05). Glycaemia value did not differ between two groups (p > 0,05). CONCLUSIONS: Group B did not reveal any differences in SpO2, HR, T and glycaemia compared to Group A. Group B showed greater values of haematocrit and bilirubin but without need of phototherapy. TRIAL REGISTRATION: Umbilical Cord Clamping: What Are the Benefits; NCT03878602. Registered 18 March 2019 retrospectively registered.

Anti-ErbB2 immunotherapeutics: struggling to make better antibodies for cancer therapy.

Over the past 3 decades, monoclonal antibodies and their related derivatives, including recently approved antibody-drug conjugates, conquered a central role in cancer therapy because of their contribution to improve survival, time to progression and quality of life of patients compared to chemotherapy protocols. This review summarizes information on approved original and biosimilar products, as well as investigational antibody-based therapeutics, targeting ErbB2. This target has been selected as a paradigmatic example because of its relevant role in sustaining the malignancy of major cancer diseases including, breast, gastric and other chemotherapy-resistant solid tumors. This work analyzes the drivers affecting research and development of next-generation anti-ErbB2 immunotherapeutics, taking into account unmet medical needs and pharmacoeconomic issues related to sustainability. The analysis may help with the design of future research and development strategies.

Predict respiratory distress syndrome by umbilical cord blood gas analysis in newborns with reassuring Apgar score.

BACKGROUND: Neonatal acidaemia at birth can increase neonatal morbidity and mortality and it is predictive of neonatal asphyxia. The umbilical blood gas analysis is a valid tool for the evaluation of neonatal acidaemia. However, umbilical cord blood gas analysis is commonly performed in high-risk situations or in the setting of Apgar scores < 7 at 5 min. METHODS: A retrospective cohort study was conducted from June to December 2018 at the Department of mother's and child's health, Poliambulanza Foundation Hospital Institute. Inclusion criteria were: full term newborns with body weight appropriate for gestational age, born by vaginal delivery or caesarean section, reassuring Apgar Score > 7 at 5 min, arterial cord blood gas analysis showing pH < 7.4 or BE <-8 mmol/l or lactate > 6 mmol/l. The aim was to evaluate the predictive role of blood gas analysis for respiratory distress syndrome in newborns with reassuring Apgar Score. RESULTS: 352 full term newborns were enrolled. Umbilical cord blood artery pH showed an association with respiratory distress syndrome (χ2(1) = 10,084, OR (95% CI): 3,9 × 10- 4(2,9 × 10- 6 - 0,048); p < 0,05). ROC curve revealed that the cut-off point of pH was 7.12, with a sensibility and specificity of 68 and 63%, respectively. CONCLUSIONS: Umbilical cord blood artery pH < 7.12 at birth is associated to respiratory distress syndrome in newborns. Blood gas analysis is an important instrument to help health care providers during assistance in the delivery room, but also to early identify newborns at high risk for respiratory distress syndrome and better manage the care of these newborns after birth.

Evaluation of pelvis postural systems in spinal cord injury patients: Outcome research.

OBJECTIVES: Compare three commercially available postural systems to determine the best for treatment of patients suffering from spinal cord injury lesion below the cervical spine. DESIGN: Outcome Research. SETTING: Ambulatory. PARTICIPANTS: Thirteen patients were recruited for this study between March 2016 and July 2016 from the Occupational Therapy clinic of "Policlinico Umberto I" hospital in Rome and Occupational Therapy of "CPO" hospital in Ostia. The patient samples consisted of eleven men (84.6%) and two women (15.4%). All the patient are suffering by SCI with a lesion below the cervical spine. INTERVENTION: We evaluate postural systems customized by three different companies. Patients tried each pelvis device for a duration of one week, after which they have been asked to fill in questionnaire concerning static stability, temperature, movement adaptability, transfers and dynamical stability during the activities of every-day life. The impact on the health status has been evaluated by means of a further questionnaire (Health Status Scale SF-12) submitted to the patients. OUTCOME MEASURES: Quality of life and daily life activities. RESULTS: The analysis of the data from the questionnaire, along with those of objective nature associated with the mapping of the pressure due to weight distribution, has allowed the selection of the most appropriate clinical solution. CONCLUSION: This study has allowed two significant conclusions: the central role of the interplay between the patient and occupational therapist in the decision role and the clear evidence that patients with spinal cord injury felt definite differences between cushion stability and were able to indicate a specific typology providing the best satisfaction.

Validation and Cross-Cultural Adaptation of the Volitional Questionnaire in an Italian Population with Psychiatric Disorders: A Cross-Sectional Study.

The aims of this study were to translate and culturally adapt the Volitional Questionnaire (VQ) into Italian and to evaluate its psychometric properties in an Italian population of patients with psychiatric disorders. The translation process from English into Italian was carried out in agreement with the authors of the original scale. The study was carried out in three psychiatric facilities, with 33 patients with psychiatric diagnoses, who were older than 18 years, and two raters (6 total) for each facility in Rome, Italy. The psychometric properties were assessed via its internal consistency, test-retest and inter-rater reliability and construct validity through comparisons with the Barthel Index, Short Form-12, Beck Depression Inventory-II and Camberwell Assessment of Need (CAN). Results showed internal consistency, using Cronbach's alpha, was significant at 0.92. In the test-retest reliability evaluation, the intraclass correlation coefficient was 0.97 and the interclass correlation coefficient was 0.99. The Spearman correlation showed significant results in the comparison with the CAN (r = -0.45, p < 0.05). These results suggest that the IT-VQ may be a valid, standardized and reliable evaluation tool that can be used to detect volitional performance improvements in a population of Italian psychiatric patients.

Construct validity, test-retest reliability, and the ability to detect change of the Canadian Occupational Performance Measure in a spinal cord injury population.

Study design: Cross-sectional study. Objectives: To examine the construct validity and the ability to detect change, of the Italian version of the Canadian Occupational Performance Measure (COPM) in a spinal cord injury (SCI) population. Settings: Rehabilitation service of the Paraplegic Center of Ostia, Italy. Methods: Thirty-nine spinal cord injury participants were recruited. The clinimetric properties of the measure were assessed following international guidelines. Cronbach's alpha and the intraclass correlation coefficient were assessed for internal consistency and test-retest reliability, respectively. Construct validity was evaluated, by calculating correlation between COPM and the Spinal Cord Independence Measure (SCIM) through Pearson's correlation coefficient and Spearman's Rho. The ability to detect change was evaluated on the overall sample. Results: The COPM was shown to be reliable in a spinal cord injury sample with positive and statistically significant results for Cronbach's alpha (0.89) and ICC (0.99 for the performance subtest and 0.98 for the satisfaction subtest). Correlation coefficients did not show a correlation between the COPM total score and the SCIM. The COPM scores improved significantly during in-patient rehabilitation, moreover the mean change between the start of treatment and the end of the therapy as evaluated with the Wilcoxon signed-rank test was -4.25 points for the performance score and -2.96 points for the satisfaction score. Conclusions: This study showed that the COPM is a reliable tool for assessing SCI clients' perceived performance of daily activities and their satisfaction with their performance.

Pseudo Prune Belly syndrome: a case report with unilateral abdominal defect.

Prune Belly syndrome occurs in 1/40,000 live births and predominantly in males. It is characterized by triad: cryptorchidism, abdominal wall, and urinary tract abnormalities. Patients with partial or unilateral abdominal wall deficiency, unilateral undescended testis, and female neonates with abdominal wall laxity are classified as Pseudo Prune Belly syndrome. In the 3%-5% of patients with Prune Belly syndrome are affected by Pseudo Prune Belly syndrome, indeed case reports available are very few. We described a case of a male patient born with a large abdominal hernia. Thoracoabdominal X-ray confirmed the large abdominal hernia and revealed a malformation of the rib cage with curved ribs. Magnetic resonance imaging showed thinning of the abdominal wall and ultrasonography detected rectus and oblique muscles hypoplastic with diastasis rectus muscles and stretching of the Hunter's line. Cryptorchidism or urinary tract abnormalities were not detected. The first surgical operation was performed at 2 years of life when the general conditions were stable.

Synthesis and preliminary in vitro evaluation of DOTA-Tenatumomab conjugates for theranostic applications in tenascin expressing tumors.

Tenatumomab is an anti-tenascin murine monoclonal antibody previously used in clinical trials for delivering radionuclides to tumors by both pre-targeting (biotinylated Tenatumomab within PAGRIT) and direct 131Iodine labeling approaches. Here we present the synthesis and in vitro characterization of three Tenatumomab conjugates to bifunctional chelating agents (NHS-DOTA, NCS-DOTA and NCS-DTPA). Results indicate ST8198AA1 (Tenatumomab-DOTAMA, derived by conjugation of NHS-DOTA), as the most promising candidate in terms of conjugation rate and yield, stability, antigen immunoreactivity and affinity. Labeling efficiency of the different chelators was investigated with a panel of cold metals indicating DOTAMA as the best chelator. Labeling of Tenatumomab-DOTAMA was then optimized with several metals and stability performed confirms suitability of this conjugate for further development. ST8198AA1 represents an improvement of the previous antibody forms because the labeling with radionuclides like 177Lu or 64Cu would allow theranostic applications in patients bearing tenascin expressing tumors.

Italian Version of the Jebsen-Taylor Hand Function Test for the Assessment of Hand Disorders: A Cross-Sectional Study.

IMPORTANCE: Having a test to evaluate hand function is fundamental to occupational therapy practice. OBJECTIVE: To assess the psychometric properties of the Italian version of the Jebsen-Taylor Hand Function Test (JTHFT). DESIGN: Cross-sectional study. SETTING: Three health care institutions in Rome, Italy. PARTICIPANTS: 136 people with injuries, burns, or neurological diseases of the hand. INTERVENTION: No intervention was provided. OUTCOMES AND MEASURES: We administered the JTHFT, an assessment of fine motor skills during performance of activities of daily living, and compared results with dynamometer readings. RESULTS: The mean ± standard deviation total time required to perform all subtests was 89.47 ± 67.98 s for the dominant hand (DH) and 167.11 ± 257.58 s for the nondominant hand (NDH). Reliability procedures were applied to data from 51 participants; mean intrarater intraclass correlation coefficient (ICC) was .814 for the DH and .981 for the NDH, and mean interrater ICC was .818 for the DH and .821 for the NDH. Pearson's correlation coefficients were significant. CONCLUSION AND RELEVANCE: Results support the use of the Italian version of the JTHFT as a measure of functional dexterity in people with upper limb disorders. WHAT THIS ARTICLE ADDS: The JTHFT is a valid and reliable assessment tool for nonspecific hand diseases. Italian health professionals can now use the JTHFT with more confidence.

Old treatments for new genetic conditions: Sirolimus therapy in a child affected by mosaic overgrowth with fibroadipose hyperplasia.

PIK3CA-related overgrowth spectrum (PROS) are overgrowth diseases involving mesenchymal tissues caused by postzygotic variants in the PIK3CA gene. Fibro-Adipose hyperplasia or Overgrowth (FAO) belongs to PROS. We reported the beneficial effect of oral low-dose sirolimus therapy in a child affected by progressive FAO in term of stabilization of the disease, good tolerability, and easy management.