Intravascular ultrasound assessment of the effect of laser energy on the arterial wall during the treatment of femoro-popliteal lesions: a CliRpath excimer laser system to enlarge lumen openings (CELLO) registry study

The CliRpath Excimer Laser System to Enlarge Lumen Openings (CELLO) registry included patients treated with modified excimer laser catheters for the endovascular treatment of peripheral artery disease affecting the superficial femoral artery (SFA) and proximal popliteal artery. The aim of this study was to assess, via intravascular ultrasound (IVUS) the dissections in the vessel wall following treatment with the laser catheters. IVUS grayscale images from the CELLO registry were systematically reviewed for dissections in the treated vessel segments by two investigators. Images from 33 patients; 66 pullbacks (1867 IVUS frames in 2 phases), were successfully matched frame-to-frame to evaluate identical segments of the treated vessels in the two phases; post-2 mm Turbo-Elite laser pilot channel creation and post Turbo-Booster laser atherectomy. Dissections were categorized as; (1) intimal, (2) medial, (3) intramural hematoma, and (4) adventitial according to the ACC Clinical Expert Consensus Document classification of dissections. An average of 57 frames was evaluated per pullback, giving a total of 3734 frames (1867 matched for pre-ablation (post channel creation) and post-ablation phases). Treatments with the modified Excimer laser catheters resulted in a significant increase in lumen area of 5.5?±?3.2-mm² (95% CI 4.3–6.8, p?<?0.0001) and reduction in plaque plus media volume of ?10.6?±?36.0 mm³ (95% CI ?25.8 to 4.6, p?=?0.1619) whilst giving rise to mainly intramural hematoma formations post Turbo-Booster laser treatment in 55% of frames assessed and 24% medial dissections with less than 1% adventitial disruption. The Excimer laser based Turbo-Booster treatment of peripheral artery lesions resulted in significant plaque debulking and increased lumen diameter with negligible degree of adventitial layer injury.     

Evidenced-Based Cognitive Rehabilitation for Persons With Multiple Sclerosis: An Updated Review of the Literature From 2007 to 2016

Objective

To update the clinical recommendations for cognitive rehabilitation of people with multiple sclerosis (MS), based on a systematic review of the literature from 2007 through 2016.

Problem-based learning in occupational therapy curriculum – implications and challenges

Purpose: Problem-based learning (PBL) is an educational method that fosters self-directed study in small groups. The purpose of this study was to describe the Tel Aviv University’s occupational therapy (OT) program and the challenges implementing such program. In addition, the study compared the PBL grades obtained by students who are native Hebrew speakers with those students who are native Arabic speakers; and, assessed the correlation between the grades in the PBL course and the grades in the clinical fieldwork studies.

Method: 166-second year OT undergraduate students participated. All completed three PBL courses and seven weeks of clinical fieldwork studies. Data collection included students’ grades in PBL course (based on PBL evaluation forms) and in clinical fieldwork studies (based on preceptor’s evaluation and a written assignment).

Results: Pearson correlations revealed significant correlations between PBL grades and clinical fieldwork studies grades. T-test analysis between students who are native Hebrew speakers and those who are native Arabic speakers revealed significant differences in PBL grades.

Conclusions: Findings imply partial congruence between students’ grades in the PBL course and their achievements in the fieldwork studies. Findings might suggest that adjustments should be made in order to assist students from minorities (challenged by language requirements) in gaining higher grades in the PBL program.

• Implications for Rehabilitation

• Problem-Based Learning (PBL) is an educational method, which fosters independent, self-directed study in small groups.

• PBL studies have the potential to prepare students for their clinical experience during studies.

• The PBL program should be adjusted for students from minorities (challenged by language requirements and different cultural backgrounds) in order to assist them in gaining more benefits from the program.

     

Varicella zoster virus in health care workers in northern Israel: seroprevalence and predictive value of history of varicella infection

Health care workers (HCWs) are susceptible to hospital acquired varicella zoster virus (VZV). We evaluated seroprevalence and predictive value of a history of varicella disease (VD) with VZV serology in HCWs in northern Israel. A total of 200 HCWs were enrolled. A high rate of seropositivity for VZV-IgG was found: 98.5% seropositive and only 1.5% seronegative. A positive history of VD was an excellent predictor for the presence of VZV-IgG; however, a negative history of VD does not rule out the presence of VZV-IgG.     

Nonpharmacologic treatment of resistant hypertensives by device-guided slow breathing exercises

BACKGROUND: Recent studies have demonstrated the antihypertensive effect of slow breathing exercises, guided interactively by a device, in patients with uncontrolled blood pressure (BP) without changing medication. This study examined the response to the same treatment protocol in resistant hypertensives. METHODS: Seventeen resistant hypertensives exercised device-guided slow breathing for 8 weeks, 15 min daily, and self-monitored BP. Data stored in the devices were collected on a PC-based system. Clinical outcomes were office and home BP changes from baseline to end values. RESULTS: Significant reductions in both office BP (-12.9/-6.9 mm Hg, P <.001 and home BP (-6.4/-2.6 mm Hg, P <.01/P <.05) without side effects with 82% responders and good compliance. CONCLUSIONS: Resistant hypertensives can benefit from and are compliant with self-treatment by device-guided slow breathing.     

Efficient maternal to neonatal transfer of antibodies against SARS-CoV-2 and BNT162b2 mRNA COVID-19 vaccine

BACKGROUNDThe significant risks posed to mothers and fetuses by COVID-19 in pregnancy have sparked a worldwide debate surrounding the pros and cons of antenatal SARS-CoV-2 inoculation, as we lack sufficient evidence regarding vaccine effectiveness in pregnant women and their offspring. We aimed to provide substantial evidence for the effect of the BNT162b2 mRNA vaccine versus native infection on maternal humoral, as well as transplacentally acquired fetal immune response, potentially providing newborn protection.METHODSA multicenter study where parturients presenting for delivery were recruited at 8 medical centers across Israel and assigned to 3 study groups: vaccinated (n = 86); PCR-confirmed SARS-CoV-2 infected during pregnancy (n = 65), and unvaccinated noninfected controls (n = 62). Maternal and fetal blood samples were collected from parturients prior to delivery and from the umbilical cord following delivery, respectively. Sera IgG and IgM titers were measured using the Milliplex MAP SARS-CoV-2 Antigen Panel (for S1, S2, RBD, and N).RESULTSThe BNT162b2 mRNA vaccine elicits strong maternal humoral IgG response (anti-S and RBD) that crosses the placenta barrier and approaches maternal titers in the fetus within 15 days following the first dose. Maternal to neonatal anti-COVID-19 antibodies ratio did not differ when comparing sensitization (vaccine vs. infection). IgG transfer ratio at birth was significantly lower for third-trimester as compared with second trimester infection. Lastly, fetal IgM response was detected in 5 neonates, all in the infected group.CONCLUSIONAntenatal BNT162b2 mRNA vaccination induces a robust maternal humoral response that effectively transfers to the fetus, supporting the role of vaccination during pregnancy.FUNDINGIsrael Science Foundation and the Weizmann Institute Fondazione Henry Krenter.     

Global microRNA profiling in favorable prognosis subgroups of cancer of unknown primary (CUP) demonstrates no significant expression differences with metastases of matched known primary tumors

No data exist on biologic differences between Cancer of unknown primary (CUP) and metastatic solid tumors of known primary site. We assigned a primary tissue of origin in 40 favorable CUP patients (A: serous peritoneal carcinomatosis n = 14, B: axillary adenocarcinoma n = 8, C: upper squamous cervical adenopathy n = 18) by means of a 64-microRNA assay. Subsequently, we profiled the expression of 733 microRNAs (miRs) in the CUP cases and compared results with metastases from 20 ovarian carcinomas, 10 breast adenocarcinomas, 20 squamous head neck or lung tumors. In the Peritoneal CUP versus Ovarian (Known Primary Metastases) KPM comparison, a total of 12 miR were significantly differentially expressed: higher than twofold expression difference in CUP was seen only for miR-513a-5p (3.7-fold upregulated) and miR-483-5p (2.5-fold upregulated), while miR-708 exhibited a twofold downregulation. In the Breast CUP versus Breast KPM comparison, only miR-29c that were downregulated in CUP by 2.7-fold satisfied the FDR threshold. miR-30e and miR-27b, downregulated in ovarian CUPs versus KPMs, were also non-significantly downregulated in breast CUP by 2.0- and 1.4-fold respectively. Six miRs, which belong to the 17–92 oncocluster showed a trend of upregulation in Breast CUP versus Breast KPM cases. A CUP signature remains elusive.     

The Involvement of Collagen Triple Helix Repeat Containing 1 in Muscular Dystrophies

Apolipoprotein E4 (APOE4) genotype is the strongest genetic risk factor for late-onset Alzheimer disease and confers a proinflammatory, neurotoxic phenotype to microglia. Here, we tested the hypothesis that bone marrow cell APOE genotype modulates pathological progression in experimental Alzheimer disease. We performed bone marrow transplants (BMT) from green fluorescent protein–expressing human APOE3/3 or APOE4/4 donor mice into lethally irradiated 5-month-old APPswe/PS1ΔE9 mice. Eight months later, APOE4/4 BMT–recipient APPswe/PS1ΔE9 mice had significantly impaired spatial working memory and increased detergent-soluble and plaque Aβ compared with APOE3/3 BMT–recipient APPswe/PS1ΔE9 mice. BMT-derived microglia engraftment was significantly reduced in APOE4/4 recipients, who also had correspondingly less cerebral apoE. Gene expression analysis in cerebral cortex of APOE3/3 BMT recipients showed reduced expression of tumor necrosis factor-α and macrophage migration inhibitory factor (both neurotoxic cytokines) and elevated immunomodulatory IL-10 expression in APOE3/3 recipients compared with those that received APOE4/4 bone marrow. This was not due to detectable APOE-specific differences in expression of microglial major histocompatibility complex class II, C-C chemokine receptor (CCR) type 1, CCR2, CX3C chemokine receptor 1 (CX3CR1), or C5a anaphylatoxin chemotactic receptor (C5aR). Together, these findings suggest that BMT-derived APOE3-expressing cells are superior to those that express APOE4 in their ability to mitigate the behavioral and neuropathological changes in experimental Alzheimer disease.Humans uniquely have three different apolipoprotein E (APOE) alleles (ɛ2, ɛ3, and ɛ4). APOE4 is the single greatest genetic risk factor for late-onset Alzheimer disease (AD), and there is a gene dosage effect.¹ However, genetic association does not inform function/pathogenesis. Multiple mechanisms have been postulated that predominantly focus on production, metabolism, or clearance of amyloid-β (Aβ) and that are variably supported by multiple observations, including: i) APOE genotype is strongly related to Aβ levels in brain and cerebrospinal fluid of AD patients^2,3; ii) modulation of apolipoprotein E (apoE) protein levels in brain results in alterations of Aβ burden^4,5; iii) Aβ degradation is at least partially apoE dependent^6,7; and iv) Aβ clearance is differentially modulated by apoE isoforms, with APOE4 mice exhibiting reduced central and peripheral Aβ clearance compared with APOE3 mice.^8–10 Aβ degradation and clearance is at least partially dependent on microglia, the innate immune effector cells of the brain. Microglia have migratory and phagocytic capacity, are increased in the vicinity of Aβ plaques, and phagocytose Aβ.^11–13 APOE genotype modulates central nervous system innate immune function in culture,¹⁴ including astrocyte and microglia elaboration of cytokines and chemokines,^15,16 microglia production of reactive oxygen species,¹⁷ microglia-mediated paracrine neurotoxicity,¹⁸ microglia migration,¹⁹ and other functions.²⁰ However, the specific contribution of microglial APOE genotype to AD pathophysiology in vivo is largely unknown.To address this critical question and to test a potential therapeutic application, we used the fact that bone marrow transplantation (BMT) results in the gradual replacement of endogenous (host) microglia (to the near exclusion of other cell types) with microglia derived from donor marrow, in both wild-type mice and transgenic mouse models of AD.^21–24 We used targeted-replacement (TR) APOE mice homozygous for either the APOE3 or APOE4 gene inserted into the mouse APOE regulatory elements^25,26 that coexpressed green fluorescent protein (GFP). We transplanted whole bone marrow (BM) isolated from TR APOE3/3;GFP or TR APOE4/4;GFP mice into lethally irradiated APPswe/PS1ΔE9 mice to determine the specific role of microglial APOE genotype in the pathological progression of AD.