Upper limb exosuit cable routing optimization.

Exosuits are emerging as promising in assisting with activities of daily living. In the design phase of an exosuit, it is fundamental to maximize its portability. The goal of this work was to identify the best cable routing configuration for an upper limb cable-driven exosuit to assist elbow flexion. Simulations were run in OpenSim. Different cable configurations were evaluated. The goal was to minimize the overall tension of the cables to reduce the device's power consumption and torque requirements. The optimal configuration was evaluated in simulation for different percentages of assistance to study its effects in terms of muscle activation and joint reaction forces. We then tested three different configurations on a test bench to both evaluate the motor current and their effect on the pronation/supination of the elbow. Simulation results suggested that a double cable configuration might help to lower the motor torque and power consumption. This conclusion was supported by the experimental results, in which the motor current was reduced by 12.5% with respect to the single cable configuration. Simulation results also showed that the optimal configuration lowered muscle activation without greatly affecting joint reactions at the elbow, even though it might cause unwanted pronation/supination, as experimental results confirmed. However, since a double configuration results in greater complexity and reduced efficiency, single-cable solutions still represent a good option.

Association of GNAS imprinting defects and deletions of chromosome 2 in two patients: clues explaining phenotypic heterogeneity in pseudohypoparathyroidism type 1B/iPPSD3.

BACKGROUND: The term pseudohypoparathyroidism (PHP) describes disorders derived from resistance to the parathyroid hormone. Albright hereditary osteodystrophy (AHO) is a disorder with several physical features that can occur alone or in association with PHP. The subtype 1B, classically associated with resistance to PTH and TSH, derives from the epigenetic dysregulation of the GNAS locus. Patients showing features of AHO were described, but no explanation for such phenotypic heterogeneity is available. An AHO-like phenotype was associated with the loss of genetic information stored in chromosome 2q37, making this genomic region an interesting object of study as it could contain modifier genes involved in the development of AHO features in patients with GNAS imprinting defects. The present study aimed to screen a series of 65 patients affected with GNAS imprinting defects, with or without signs of AHO, for the presence of 2q37 deletions in order to find genes involved in the clinical variability. RESULTS: The molecular investigations performed on our cohort of patients with GNAS imprinting defects identified two overlapping terminal deletions of the long arm of chromosome 2. The smaller deletion was of approximately 3 Mb and contained 38 genes, one or more of which is potentially involved in the clinical presentation. Patients with the deletions were both affected by a combination of the most pathognomic AHO-like features, brachydactyly, cognitive impairment and/or behavioural defects. Our results support the hypothesis that additional genetic factors besides GNAS methylation defects are involved in the development of a complex phenotype in the subgroup of patients showing signs of AHO. CONCLUSIONS: For the first time, the present work describes PHP patients with hormone resistance and AHO signs simultaneously affected by GNAS imprinting defects and 2q37 deletions. Although further studies are needed to confirm the cause of these two rare molecular alterations and to identify candidate genes, this finding provides novel interesting clues for the identification of factors involved in the still unexplained clinical variability observed in PHP1B.

Systematic review of nonpharmacological analgesic interventions for common needle­related procedure in newborn infants and development of evidence­based clinical guidelines

The aim of this literature review was to develop clinical guidelines for the prevention and control of needle­related pain in newborn infants. The guidelines were developed by the Italian Society of Neonatology, using the Grading of Recommendations, Assessment, Development and Evaluation approach, based on the assessment of 232 papers published between 1986 and 2015. The quality of the evidence was high or moderate for some behavioural and nonpharmacological interventions.

Systematic review of nonpharmacological analgesic interventions for common needle­related procedure in newborn infants and development of evidence­based clinical guidelines

The aim of this literature review was to develop clinical guidelines for the prevention and control of needle-related pain in newborn infants. The guidelines were developed by the Italian Society of Neonatology, using the Grading of Recommendations, Assessment, Development and Evaluation approach, based on the assessment of 232 papers published between 1986 and 2015. The quality of the evidence was high or moderate for some behavioural and nonpharmacological interventions. CONCLUSION: There was sufficient evidence to strongly support the use of nonpharmacological interventions for common needle-related procedures in newborn infants. Combined interventions seemed to be more effective in relieving procedural pain

The Complex GNAS Imprinted Locus and Mesenchymal Stem Cells Differentiation.

All tissues and organs derive from stem cells, which are undifferentiated cells able to differentiate into specialized cells and self-renewal. In mammals, there are embryonic stem cells that generate germ layers, and adult stem cells, which act as a repair system for the body and maintain the normal turnover of regenerative organs. Mesenchymal stem cells (MSCs) are nonhematopoietic adult multipotent cells, which reside in virtually all postnatal organs and tissues, and, under appropriate in vitro conditions, are capable to differentiate into osteogenic, adipogenic, chondrogenic, myogenic, and neurogenic lineages. Their commitment and differentiation depend on several interacting signaling pathways and transcription factors. Most GNAS-based disorders have the common feature of episodic de novo formation of islands of extraskeletal, qualitatively normal, bone in skin and subcutaneous fat. The tissue distribution of these lesions suggests that pathogenesis involves abnormal differentiation of MSCs and/or more committed precursor cells that are present in subcutaneous tissues. Data coming from transgenic mice support the concept that GNAS is a key factor in the regulation of lineage switching between osteoblast and adipocyte fates, and that its role may be to prevent bone formation in tissues where bone should not form. Despite the growing knowledge about the process of heterotopic ossification in rare genetic disorders, the pathophysiological mechanisms by which alterations of cAMP signaling lead to ectopic bone formation in the context of mesenchymal tissues is not fully understood.

Pain management during invasive procedures at Italian NICUs: has anything changed in the last five years?

OBJECTIVE: To ascertain the extent to which neonatal analgesia for invasive procedures has changed in the last 5 years since the publication of Italian guidelines. METHODS: We compared survey data for the years 2004 and 2010 on analgesia policy and practices for common invasive procedures at Italian Neonatal Intensive Care Units (NICUs); 75 NICUs answered questionnaires for both years and formed the object of this analysis. RESULTS: By 2010 analgesia practices for procedural pain had improved significantly for almost all invasive procedures (p < 0.05), both non-pharmacological and pharmacological methods being adopted by the majority of NICUs (unlike the situation in 2004). The routine use of medication for major invasive procedures was still limited, however (35% of lumbar punctures, 40% of tracheal intubations, 46% during mechanical ventilation). Postoperative pain treatment was still inadequate, and 41% of facilities caring for patients after surgery did not treat pain routinely. Pain monitoring had definitely improved since 2004 (p < 0.05), but not enough: only 21% and 17% of NICUs routinely assess pain during mechanical ventilation and after surgery, respectively. CONCLUSION: There have been improvements in neonatal analgesia practices in Italy since national guidelines were published, but pain is still undertreated and underscored, especially during major invasive procedures. It is mandatory to address the gap between the recommendations in the guidelines and clinical practice must be addressed through with effective quality improvement initiatives.

[Italian guidelines and recommendations for prevention and treatment of pain in the newborn]. / Linee-guida e raccomandazioni per la prevenzione ed il trattamento del dolore nel neonato.

OBJECTIVE: Despite accumulating evidence that procedural pain experienced by preterm infants may have acute detrimental and even long-term effects on an infant's subsequent behavior and neurological outcome, neonates admitted to Neonatal Intensive Care Units still frequently experience acute and prolonged uncontrolled pain. Many invasive and surgical procedures are routinely performed at the bedside in the NICU without adequate pain management. AIM: To develop evidence-based guidelines and recommendations for pain control and prevention in Italian i.e. heel lancing, venipuncture and percutaneous venous line positioning, tracheal intubation, mechanical ventilation, lumbar puncture, chest tube positioning, for certain surgical procedures performed at the NICU, e.g. central venous cutdown, surgical PDA ligation, and cryotherapy, laser therapy for ROP, and for postoperative pain management. CONCLUSION: Adequate pain prevention and management should be an essential part of standard health care at the NICU, and recognizing and assessing sources of pain should be routine in the day-to-day practice of physicians and nurses taking care of the newborn. We hope these guidelines will contribute towards increasing the NICU caregiver's awareness and understanding of the importance of adequate pain control and prevention.

Efficacy and tolerability of moexipril and nitrendipine in postmenopausal women with hypertension. MADAM study group. Moexipril as Antihypertensive Drug After Menopause.

OBJECTIVE: The aim of this study was to compare the efficacy and tolerability of the new angiotensin-converting enzyme (ACE) inhibitor moexipril and the calcium antagonist nitrendipine in postmenopausal women with mild to moderate hypertension. METHODS: After a 4-week placebo run-in period, 93 postmenopausal women (age range 44-70 years) with primary hypertension were randomized to receive moexipril 15 mg once daily or nitrendipine 20 mg once daily for 8 weeks. The mean sitting systolic (SSBP) and sitting diastolic blood pressures (SDBP) at baseline were 161.3/103.0 mmHg in the moexipril group, and 162.2/102.3 mmHg in the nitrendipine group. RESULTS: After the 8 weeks of treatment, the SSBP/SDBP reductions were -21.2/-15.2 mmHg in the moexipril group and -18.2/-13.6 mmHg in the nitrendipine group. Blood pressure responses were adequate in 82.2% of the moexipril-treated patients and in 80.9% in the nitrendipine-treated group. Adverse events were more frequent with nitrendipine than with moexipril. The most common adverse events in the nitrendipine group were headache (23.4%), flushing (21.3%) and ankle oedema (14.9%). In the moexipril group the most common adverse event was cough (8.9%). CONCLUSION: The results of the study suggest that moexipril and nitrendipine are equieffective in the given dosages. In the patient population of postmenopausal women, the ACE inhibitor moexipril appears to have an advantage over the calcium antagonist nitrendipine with regard to tolerability.

Stimulation of cytotoxic and non-cytotoxic functions of natural killer cells by bacterial membrane proteoglycans and ribosomes.

The present study was designed to investigate the effect of membrane proteoglycans (MPG) from Klebsiella pneumoniae on the function of human natural killer (NK) cells. MPG combined with bacterial ribosomes from Klebsiella pneumoniae, Streptococcus pneumoniae, Streptococcus pyogenes and Haemophilus influenzae, constitute a bacterial immunomodulator (MS D 53), currently in clinical use. Human peripheral blood lymphocytes (PBL) exposed in vitro to MPG or MS D 53 for 20 h showed enhanced NK cytotoxicity. Augmentation of NK cytotoxicity depended upon a direct effect on NK cells, inasmuch as these compounds were also effective on highly purified large granular lymphocytes (LGL). We also studied the effects of MPG on non-cytotoxic functions of NK cells, namely in vitro locomotion and production of IL-1. MPG (and MS D 53) induced IL-1 release in LGL. Moreover, MPG-treated LGL showed enhanced locomotory activity, as assessed by measuring the penetration into nitrocellulose filters. The capacity of MPG (and MS D 53) to activate cytotoxic and noncytotoxic functions of NK cells may contribute to enhancement of nonspecific resistance in vivo after treatment with this agent.

Activated adherent large granular lymphocytes/natural killer (LGL/NK) cells change their migratory behaviour.

Unstimulated large granular lymphocytes/natural killer (LGL/NK) cells, unlike small T lymphocytes, exhibit prompt locomotion into nitrocellulose filters in response to chemo-attactrants, but, unlike monocytes, are unable to migrate as adherent cells across polycarbonate filters. Upon activation with 4-B-phorbol 12,13 dibutyrate (PDBU), LGL/NK cells become adherent and change their migratory behaviour, having the ability to migrate as adherent cells across polycarbonate filters. PDBU-treated high-density T lymphocytes did not show, under the same conditions, locomotory activity. The change in migratory behaviour following activation may represent an important determinant of the ability of activated LGL/NK cells to adhere to vascular linings and localize in tissues.

c-fos proto-oncogene expression in human NK/LGL cells: expression is not constitutive and is associated with functional activation.

Unlike mature myeloid and monocytic cells and cell lines committed to terminal myelomonocytic differentiation, highly purified preparations of human natural killer cells/large granular lymphocytes (NK/LGL) did not spontaneously express the c-fos proto-oncogene. Transient expression of c-fos in NK/LGL was associated with functional activation with IL-2, IFN-gamma, LPS and PMA, which increased their cytotoxic activity, lymphokine secretion and in vitro chemotaxis. These results, together with the finding that T-cell receptor genes are in germ-line configuration in the vast majority of peripheral blood NK/LGL, are compatible with the hypothesis that these cells represent a separate hematopoietic lineage.

The use of human fibrin glue and of the suture in polyglactin 910 in extraintracranial by-pass.

At the Division of Neurosurgery of Fatebenefratelli-Oftalmico Hospital in Milano, 12 of the last 22 temporosylvian anastomosis have been performed employing sutures with separate points in mixed materials, partly nylon and partly Polyglactin 910 (reabsorbable) in order to avoid as much as possible the disadvantages of permanent sutures; in the other 10 consecutive cases reducing about 50% the points of suture and employing human fibrin glue as complement of the suture, in order to respect better the arterial wall and to reduce significantly the critical times of the operation (clampage). The Authors compared the clinical and instrumental results of the patients of this series with the ones of a previous series operated with traditional technique and pointed out a better success in the last operations (mixed materials and fibrin glue).

Myelokathexis associated with multiple congenital malformations: immunological study on phagocytic cells and lymphocytes.

A 5-year-old boy was first seen at the age of 11 months when he presented with growth retardation, skeletal dysmorphisms and neutropenia. Since then he has remained leukopenic except when he has pulmonary infections with a marked leukocytosis. Despite his neutropenia, marked myeloid hyperplasia was evident on marrow smear examination; many cells showed abnormally hypersegmented nuclei, with unusual shape or pyknotic nuclei. Phagocytic cells showed impaired phagocytosis, candidacidal activity, metabolic burst and chemotaxis. Moreover, the patient's serum generated less chemotactic activity than normal serum. These data indicate a selectively complex defect of the neutrophil during differentiation associated with the presence of an inhibitor of chemotactic factors in the patient's serum.

T cell receptor (alpha, beta, gamma) gene rearrangements and expression in normal and leukemic large granular lymphocytes/natural killer cells.

The large granular lymphocyte (LGL) population, which effects a natural killer (NK) function, consists of cells whose lineage derivation has not been clearly established on the basis of phenotypic and functional properties. To clarify the relationship of LGL/NK cells to T cells we studied patterns of rearrangement and expression of the T cell receptor (Ti) genes alpha, beta, and gamma in normal human LGLs; in CD8+, CD8-, Mol+, and Mol- LGL subsets; and in 17 cases of leukemic LGL proliferations (T gamma LPD). T alpha, T beta, and T gamma genes were not expressed, nor were T beta and T gamma genes rearranged in normal LGLs or LGL subsets. The T gamma LPD were divided into two groups. One group (15/17 cases) was characterized as CD3+ and displayed Ti gene rearrangements. Seven of these cases were reactive with monoclonal antibody WT31, which suggested expression of an alpha/beta heterodimer on the cell surface. The other group (2/17 cases) was CD3- with unrearranged Ti genes. These results indicate that the normal LGL/NK population is homogeneous and distinct from the normal T cell population because it does not express, and as a result, cannot effect its immune function through the T cell receptor molecules. Conversely, T gamma LPDs represent a heterogeneous group of lymphoproliferative diseases within which the CD3-, Ti- cases most likely represent the neoplastic counterpart of normal LGL cells. The more frequent CD3+ cases may be related to recently described NK-like T cells. The observations that normal LGLs maintain germline T gamma genes and that many CD3+ T gamma LPD display an alpha/beta heterodimer suggest that a T gamma-containing receptor may not be necessary for NK or NK-like cytotoxicity.

T-cell receptor gene rearrangements and expression in normal human large granular lymphocytes (LGL) and their pathological expansions.

The lineage to which normal large granular lymphocytes/natural killer (LGL/NK) cells belong is controversial; in fact they share some surface markers and functional activities with monocytes, but also with T lymphocytes. The relationship of LGL to the T cell lineage by analysis with the T cell receptor (T-rec) gene has been investigated. Pure preparations of human LGL and their CD11(+) CD8(-) and CD11(-) CD8(+) subsets had the Tß gene in its unrearranged germline configuration. Expression of Tα and Tß genes was not detectable. The organization of Tγ gene, which is of particular importance because it occurs early in T cell ontogeny, was also found in its germline configuration.A rare type of lymphoproliferative disorder, termed Tγ-LPD, is characterized by expansion of cells very similar to LGL for morphology, phenotype, and functional activity. Of 17 patients with Tγ-LPD studied for T-rec rearrangement, 15 displayed rearrangement of Tß and Tγ loci and were CD3+ (14/15 had monoclonal rearrangement), while 2 cases were in germline configuration and were CD3-. Similarly to very small subsets of CD3+ LGL recently described, most Tγ-LPD cases are CD3+ and have T-rec genes rearranged. These data suggest that either a subset of LGL or a particular step of differentiation may be related to the T cell lineage; they also demonstrate that, in contrast to previous views, most TγLPD are monoclonal, presumably neoplastic, lymphoproliferative disorders.