Baseline malaria prevalence and care-seeking behaviours in rural Madagascar prior to a trial to expand malaria community case management to all ages.

Background: Integrated community case management of malaria, pneumonia, and diarrhoea can reduce mortality in children under five years (CU5) in resource-poor countries. There is growing interest in expanding malaria community case management (mCCM) to older individuals, but limited empirical evidence exists to guide this expansion. As part of a two-year cluster-randomized trial of mCCM expansion to all ages in southeastern Madagascar, a cross-sectional survey was conducted to assess baseline malaria prevalence and healthcare-seeking behaviours.

AOSpine Consensus Paper on Nomenclature for Working-Channel Endoscopic Spinal Procedures.

Study Design: International consensus paper on a unified nomenclature for full-endoscopic spine surgery.

Objectives: Minimally invasive endoscopic spinal procedures have undergone rapid development during the past decade. Evolution of working-channel endoscopes and surgical instruments as well as innovation in surgical techniques have expanded the types of spinal pathology that can be addressed.

Regional variations in acceptance, and utilization of minimally invasive spinal surgery techniques among spine surgeons: results of a global survey.

Background: Regional differences in acceptance and utilization of MISST by spine surgeons may have an impact on clinical decision-making and the surgical treatment of common degenerative conditions of the lumbar spine. The purpose of this study was to analyze the acceptance and utilization of various minimally invasive spinal surgery techniques (MISST) by spinal surgeons the world over.

Methods: The authors solicited responses to an online survey sent to spine surgeons by email, and chat groups in social media networks including Facebook, WeChat, WhatsApp, and Linkedin.

Surgeon motivation, and obstacles to the implementation of minimally invasive spinal surgery techniques.

Background: This study aimed to analyze the motivators and obstacles to the implementation of minimally invasive spinal surgery techniques (MISST) by spinal surgeons. Motivators and detractors may impact the availability of MISST to patients and drive spine surgeons' clinical decision-making in the treatment of common degenerative conditions of the lumbar spine.

Methods: The authors solicited responses to an online survey sent to spine surgeons by email, and chat groups in social media networks including Facebook, WeChat, WhatsApp, and Linkedin.

Surgeon training and clinical implementation of spinal endoscopy in routine practice: results of a global survey.

Background: Training of spine surgeons may impact the availability of contemporary minimally invasive spinal surgery (MIS) to patients and drive spine surgeons' clinical decision-making when applying minimally invasive spinal surgery techniques (MISST) to the treatment of common degenerative conditions of the lumbar spine. Training requirements and implementation of privileges vary in different parts of the world. The purpose of this study was to analyze the training in relation to practice patterns of surgeons who perform lumbar endoscopic spinal surgery the world over.

Combined evaluation of LC3B puncta and HMGB1 expression predicts residual risk of relapse after adjuvant chemotherapy in breast cancer.

In spite of adjuvant chemotherapy, a significant fraction of patients with localized breast cancer (BC) relapse after optimal treatment. We determined the occurrence of cytoplasmic MAP1LC3B/LC3B (microtubule-associated protein 1 light chain 3B)-positive puncta, as well as the presence of nuclear HMGB1 (high mobility group box 1) in cancer cells within surgical BC specimens by immunohistochemistry, first in a test cohort (152 patients) and then in a validation cohort of localized BC patients who all received adjuvant anthracycline-based chemotherapy (1646 patients). Cytoplasmic LC3B(+) puncta inversely correlated with the intensity of SQSTM1 staining, suggesting that a high percentage cells of LC3B(+) puncta reflects increased autophagic flux.

Clinical impact of the NKp30/B7-H6 axis in high-risk neuroblastoma patients.

The immunosurveillance mechanisms governing high-risk neuroblastoma (HR-NB), a major pediatric malignancy, have been elusive. We identify a potential role for natural killer (NK) cells, in particular the interaction between the NK receptor NKp30 and its ligand, B7-H6, in the metastatic progression and survival of HR-NB after myeloablative multimodal chemotherapy and stem cell transplantation. NB cells expressing the NKp30 ligand B7-H6 stimulated NK cells in an NKp30-dependent manner.

Antitumor immunity triggered by melphalan is potentiated by melanoma cell surface-associated calreticulin.

Systemic chemotherapy generally has been considered immunosuppressive, but it has become evident that certain chemotherapeutic drugs elicit immunogenic danger signals in dying cancer cells that can incite protective antitumor immunity. In this study, we investigated whether locoregionally applied therapies, such as melphalan, used in limb perfusion for melanoma (Mel-ILP) produce related immunogenic effects. In human melanoma biopsies, Mel-ILP treatment upregulated IL1B, IL8, and IL6 associated with their release in patients' locoregional sera.

Viral envelope is a major determinant of enhanced fitness of a multidrug-resistant HIV-1 variant.

Multidrug-resistant (MDR) HIV-1 viruses are thought to be less pathogenic than wild-type viruses because of the fitness costs of drug-resistance mutations. However, we identified an individual infected with MDR virus associated with rapid disease progression referred to as MDR-1. To study the contribution of virologic factors to rapid disease progression, we constructed molecular clones that demonstrated high replication fitness and cytopathicity.

A randomized open-label study of 3- versus 5-drug combination antiretroviral therapy in newly HIV-1-infected individuals.

Background: To understand whether combination antiretroviral therapy (cART) has been optimized, we asked whether 3-drug protease inhibitor (PI)-based cART intensified with raltegravir and maraviroc and initiated during early infection would improve outcomes when compared with similarly applied 3-drug PI-based cART.

Methods: Forty newly HIV-1-infected patients were randomized 1:2 to receive 3-drug (N = 14) or 5-drug (N = 26) therapy. The primary end point was the percent of subjects with undetectable plasma viremia using standard reverse transcriptase-polymerase chain reaction and the single copy assay after 48 weeks.

Defective immunogenic cell death of HMGB1-deficient tumors: compensatory therapy with TLR4 agonists.

Immunogenic cell death induced by anticancer chemotherapy is characterized by a series of molecular hallmarks that include the exodus of high-mobility group box 1 protein (HMGB1) from dying cells. HMGB1 is a nuclear nonhistone chromatin-binding protein. It is secreted at the late stages of cellular demise and engages Toll-like receptor4 (TLR4) on dendritic cells (DCs) to accelerate the processing of phagocytic cargo in the DC and to facilitate antigen presentation by DC to T cells.

Analysis of NKp30/NCR3 isoforms in untreated HIV-1-infected patients from the ANRS SEROCO cohort.

Natural killer (NK) cells play a prominent role at the intersection between innate and cognate immunity, thus influencing the development of multiple pathological conditions including HIV-1-induced AIDS. Not only NK cells directly kill HIV-1-infected cells, but also control the maturation and/or elimination of dendritic cells (DCs). These functions are regulated by the delicate balance between activating and inhibiting receptors expressed at the NK-cell surface.

Clinical results of XMR-assisted percutaneous transforaminal endoscopic lumbar discectomy.

Background: Although percutaneous endoscopic lumbar discectomy (PELD) has shown favorable outcomes in the majority of lumbar discectomy cases, there were also some failures. The most common cause of failure is the incomplete removal of disc fragments. The skin entry point for the guide-needle trajectory and the optimal placement of the working sleeve are largely blind, which might lead to the inadequate removal of disc fragments.

Percutaneous endoscopic lumbar herniectomy for high-grade down-migrated L4-L5 disc through an L5-S1 interlaminar approach: a technical note.

Background: L4-L5 disc herniations can be treated with percutaneous endoscopic lumbar discectomy (PELD) using a transforaminal posterolateral approach. Although PELD has some distinct advantages over conventional open discectomy, inadequate decompression is a major cause of failure of the procedure, especially with high-grade migrations. The objective of this technical note is to present a new surgical approach for treating high-grade, down-migrated, L4-L5 disc herniations through an L5-S1 interlaminar endoscopic approach.

Transcorporeal tunnel approach for unilateral cervical radiculopathy: a 2-year follow-up review and results.

Background: The long-term complications of traditional discectomy and fusion surgery have led to the need for minimally invasive procedures that do not require a complete discectomy and fusion. Jho developed an anterior unco-foraminotomy that we have modified, with the approach being more medial than that of Jho, into an anterior transcorporeal tunnel approach which we use for cervical spondylotic unilateral radiculopathy.

Methods: A retrospective analysis was carried out in 30 patients who underwent a transcorporeal "tunnel" anterior micro-foraminotomy for unilateral radicular symptoms with a follow-up more than 2 years.

Novel integrase inhibitors for HIV.

Importance Of The Field: Integrase inhibitors are the newest class of antiretroviral agents developed to treat HIV-1 infection. Raltegravir (RAL), the only integrase inhibitor (INI) currently approved for the treatment of HIV-infected patients, has proven to be a potent and well-tolerated antiretroviral (ARV) agent. It is currently approved and used for the treatment of both ARV-experienced and ARV-naive patients.

Risk of developing seizure after percutaneous endoscopic lumbar discectomy.

Study Design: A retrospective analysis in patients who underwent percutaneous endoscopic lumbar discectomy (PELD) and developed seizures during the procedure; and to identify the risk of developing seizure during PELD by measuring cervical epidural pressure.

Objective: To evaluate clinical significance, characteristics, and risk factors for developing seizure and neck pain in patients undergoing PELD.

Summary And Background Data: Increased epidural pressure during PELD has been reported earlier.

Modified transcorporeal anterior cervical microforaminotomy assisted by O-arm-based navigation: a technical case report.

This study was done to present our surgical experience of modified transcorporeal anterior cervical microforaminotomy (MTACM) assisted by the O-arm-based navigation system for the treatment of cervical disc herniation. We present eight patients with foraminal disc herniations at the C5-C6, C6-C7, and C7-T1 levels. All patients had unilateral radicular arm pain and motor weakness.

Natural polymorphisms of human immunodeficiency virus type 1 integrase and inherent susceptibilities to a panel of integrase inhibitors.

We evaluated the human immunodeficiency virus type 1 (HIV-1) integrase coding region of the pol gene for the presence of natural polymorphisms in patients during early infection (AHI) and with triple-class drug-resistant HIV-1 (MDR). We analyzed selected recombinant viruses containing patient-derived HIV-1 integrase for susceptibility to a panel of strand transfer integrase inhibitors (InSTI). A pretreatment sequence analysis of the integrase coding region was performed for 112 patients identified during acute or early infection and 15 patients with triple-class resistance.

Drug-susceptible HIV-1 infection despite intermittent fixed-dose combination tenofovir/emtricitabine as prophylaxis is associated with low-level viremia, delayed seroconversion, and an attenuated clinical course.

Background: Continued high rates of HIV-1 transmission have fueled interest in the use of antiretrovirals to prevent infection. Attenuated infection with failure of tenofovir as prophylaxis has been reported in animal models. Here, we report a case of HIV-1 infection despite intermittent use of fixed-dose combination tenofovir and emtricitabine (FTC).

Homeostatic cytokines and expansion of regulatory T cells accompany thymic impairment in children with Down syndrome.

Down syndrome (DS), the most common chromosomal abnormality in humans, is characterized by precocious immunologic aging that results, among other things, in alterations of B and T lymphocyte subsets and natural killer cells, defective phagocytosis, and chemotaxis of polymorphonuclear leukocytes. We studied 30 children affected by DS, compared them to 29 healthy controls, and evaluated the functionality of the thymus (by measuring the amount of lymphocytes that express the signal-joint T cell receptor rearrangement excision circles [sj-TREC+]), the plasma levels of interleukin (IL)-7 and IL-15, the proliferative T cell response to these cytokines, the expression of the alpha chain of the IL-7 receptor (CD127), the extrathymic differentiation of T lymphocytes, and the presence of natural regulatory T cells (Tregs) in peripheral blood. We found that DS children had a significantly lower number of sj-TREC+ lymphocytes, the levels of which were strongly correlated with age.

Mitochondrial alterations and tendency to apoptosis in peripheral blood cells from children with Down syndrome.

Different types of cells from subjects with Down syndrome (DS) have an increased susceptibility to cell death. We have studied apoptosis and mitochondrial (mt) membrane potential (DeltaPsi(m)) in peripheral blood mononuclear cells (PBMC) from DS children and age-matched healthy donors after in vitro treatment with apoptogenic molecules, along with mtDNA content. We found that PBMC from DS and healthy controls had a similar tendency to undergo apoptosis and a similar amount of mtDNA.

Characterization of cells with different mitochondrial membrane potential during apoptosis.

Background: Until now, the simultaneous analysis of several parameters during apoptosis, including DNA content and mitochondrial membrane potential (DeltaPsi), has not been possible because of the spectral characteristics of the commonly used dyes. Using polychromatic flow cytometry based upon multiple laser and UV lamp excitation, we have characterized cells with different DeltaPsi during apoptosis.

Methods: U937 cells were treated with the flavonoid quercetin (Qu) and stained with JC-1 to detect DeltaPsi, propidium iodide (PI) for cell viability, Hoechst 33342 for DNA content, Annexin V conjugated with Alexa Fluor-647 for detection of phosphatidilserine (PS) exposure, marker of early apoptosis, or Mitotracker Deep Red for the determination of mitochondrial mass.

MMP-7 promoter polymorphisms do not influence CD4+ recovery and changes in plasma viral load during antiretroviral therapy for HIV-1 infection.

Matrix metalloproteinase-7 (MMP-7) generates soluble Fas Ligand (FasL), which is involved in the apoptotic loss of CD4+ T cells during HIV infection. We evaluated whether two polymorphisms in MMP-7 promoter could influence CD4+ recover in response to antiretroviral therapy, and found that these polymorphisms are ineffective.