Potential of conventional & bispecific broadly neutralizing antibodies for prevention of HIV-1 subtype A, C & D infections.

There is great interest in passive transfer of broadly neutralizing antibodies (bnAbs) and engineered bispecific antibodies (Abs) for prevention of HIV-1 infections due to their in vitro neutralization breadth and potency against global isolates and long in vivo half-lives. We compared the potential of eight bnAbs and two bispecific Abs currently under clinical development, and their 2 Ab combinations, to prevent infection by dominant HIV-1 subtypes in sub-Saharan Africa. Using in vitro neutralization data for Abs against 25 subtype A, 100 C, and 20 D pseudoviruses, we modeled neutralization by single Abs and 2 Ab combinations assuming realistic target concentrations of 10μg/ml total for bnAbs and combinations, and 5μg/ml for bispecifics.

Managing the Burden of Non-NASH NAFLD.

Purpose Of Review: The purpose of this review article is to raise awareness of the significance of steatosis that exist within the spectrum of nonalcoholic fatty liver disease (NAFLD). While the impact of nonalcoholic steatohepatitis (NASH), and its potential for histologic progression to cirrhosis and hepatocellular carcinoma is widely appreciated, the impact of non-NASH NAFLD (steatosis) on morbidity and mortality is less well recognized.

Recent Findings: NAFLD is a spectrum of hepatic pathology with a rising prevalence worldwide.

Altered N170 and mood symptoms in bipolar disorder: An electrophysiological study of configural face processing.

Objectives: Altered social behavior during mood episodes in bipolar disorder often has detrimental and long-lasting interpersonal consequences. Abnormal face processing may play a role in linking brain functions to clinical symptoms and behavior. This study aimed to understand configural face processing in bipolar disorder as a function of basic communicative attributes of the face and mood symptoms using event-related brain potentials (ERPs).

Markers of Microbial Translocation and Immune Activation Predict Cognitive Processing Speed in Heavy-Drinking Men Living with HIV.

HIV infection and alcohol use disorder are associated with deficits in neurocognitive function. Emerging evidence points to pro-inflammatory perturbations of the gut-brain axis as potentially contributing to neurocognitive impairment in the context of HIV and chronic heavy alcohol use. This study examined whether plasma markers of microbial translocation (LPS) from the gastrointestinal tract and related immune activation (sCD14, EndoCAb) were associated with neurocognition in 21 men living with HIV who were virally suppressed on antiretroviral therapy.

[The association between allergic rhinitis control and sleep quality].

Background: Allergic rhinitis (AR) is the most common form of atopic disease, comprising 50% of atopic diseases. Recently, this disease has increasingly been the focus of intensive research. Previous work has shown that AR has a significant impact on sleep quality.

Adjuvant treatment for pancreatic ductal carcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a tumor with a very poor prognosis. Most of the patients are diagnosed in advanced stages of the disease, and 5-year survival rates in these patients remains <10%. Surgery still remains the only radical treatment option, although only 15-20% of patients are candidates for surgical resection at the time of the diagnosis.

Neoadjuvant treatment for borderline and resectable pancreatic ductal adenocarcinoma.

Nowadays and given the improvement in response rate with the new schemes of treatment with chemotherapy, the interest in neoadjuvant treatment for pancreatic ductal adenocarcinoma, allowing the early application of systemic therapies, has also increased. However, treatment selection fundamentally depends on decisions taken by multidisciplinary committees due to the absence of randomized trials on this indication and because the available evidence is based primarily on small studies. The present manuscript tries to establish recommendations based on the available evidence and expert opinion to correctly select the indication, the type of treatment, as well as its duration and how to correctly follow-up patients during treatment with chemotherapy.

Breast Density Legislation in New England: A Survey Study of Practicing Radiologists.

Rationale And Objectives: This study aimed to assess radiologists' knowledge about breast density legislation as well as perceived practice changes resulting from the enactment of breast density legislation.

Materials And Methods: This is an institutional review board-exempt anonymous email survey of 523 members of the New England Roentgen Ray Society. In addition to radiologist demographics, survey questions addressed radiologist knowledge of breast density legislation, knowledge of breast density as a risk factor for breast cancer, recommendations for supplemental screening, and perceived practice changes resulting from density notification legislation.

Transcranial Magnetic and Direct Current Stimulation in Children.

Promising results in adult neurologic and psychiatric disorders are driving active research into transcranial brain stimulation techniques, particularly transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), in childhood and adolescent syndromes. TMS has realistic utility as an experimental tool tested in a range of pediatric neuropathologies such as perinatal stroke, depression, Tourette syndrome, and autism spectrum disorder (ASD). tDCS has also been tested as a treatment for a number of pediatric neurologic conditions, including ASD, attention-deficit/hyperactivity disorder, epilepsy, and cerebral palsy.

Systems serology for evaluation of HIV vaccine trials.

The scale and scope of the global epidemic, coupled to challenges with traditional vaccine development approaches, point toward a need for novel methodologies for HIV vaccine research. While the development of vaccines able to induce broadly neutralizing antibodies remains the ultimate goal, to date, vaccines continue to fail to induce these rare humoral immune responses. Conversely, growing evidence across vaccine platforms in both non-human primates and humans points to a role for polyclonal vaccine-induced antibody responses in protection from infection.

Transcatheter Mitral Valve Replacement for Patients With Symptomatic Mitral Regurgitation: A Global Feasibility Trial.

Background: Symptomatic mitral regurgitation (MR) is associated with high morbidity and mortality that can be ameliorated by surgical valve repair or replacement. Despite this, many patients with MR do not undergo surgery. Transcatheter mitral valve replacement (TMVR) may be an option for selected patients with severe MR.

Selection bias: Examining the feasibility, utility, and participant receptivity to incorporating simulation into the general surgery residency selection process.

Background: Opportunities exist to revise the current residency selection process to capture desirable candidate competencies. We examined the extent to which components of the American College of Surgeons/Association for Surgical Education simulation-based medical student curriculum combined with a teamwork activity could be used as potential screening method.

Methods: Students participated in a workshop consisting of training/evaluation of knot tying, suturing, airway management, gowning/gloving, and teamwork.

Differences in Trabecular Microstructure Between Black and White Women Assessed by Individual Trabecular Segmentation Analysis of HR-pQCT Images.

Black women have lower fracture risk compared with white women, which may be partly explained by improved volumetric bone mineral density (vBMD) and bone microarchitecture primarily within the cortical bone compartment. To determine if there are differences in trabecular microstructure, connectivity, and alignment according to race/ethnicity, we performed individual trabecular segmentation (ITS) analyses on high-resolution peripheral quantitative computed tomography (HR-pQCT) scans of the distal radius and tibia in 273 peri- and postmenopausal black (n = 100) and white (n = 173) women participating in the Study of Women's Health Across the Nation in Boston. Unadjusted analyses showed that black women had greater trabecular plate volume fraction, plate thickness, plate number density, and plate surface area along with greater axial alignment of trabeculae, whereas white women had greater trabecular rod tissue fraction (p < 0.

Acute Kidney Injury in Hematopoietic Stem Cell Transplantation: A Review.

Hematopoietic stem cell transplantation (HSCT) is a highly effective treatment strategy for lymphoproliferative disorders and bone marrow failure states including aplastic anemia and thalassemia. However, its use has been limited by the increased treatment related complications, including acute kidney injury (AKI) with an incidence ranging from 20% to 73%. AKI after HSCT has been associated with an increased risk of mortality.

Differences by HIV serostatus in coronary artery disease severity and likelihood of percutaneous coronary intervention following stress testing.

Background: HIV-infected persons develop coronary artery disease (CAD) more commonly and earlier than uninfected persons; however, the role of non-invasive testing to stratify CAD risk in HIV is not well defined.

Methods And Results: Patients were selected from a single-center electronic cohort of HIV-infected patients and uninfected controls matched 1:2 on age, sex, race, and type of cardiovascular testing performed. Patients with abnormal echocardiographic or nuclear stress testing who subsequently underwent coronary angiography were included.

The Associations Between Forced Sex and Severe Mental Health, Substance Use, and HIV Risk Behaviors Among Asian American Women.

We examined the association between forced sex history and mental health, sexual health, and substance use among Asian American women ( n = 720); 14.3% of our sample ( n = 103) reported forced sex experiences. Multiple logistic regression analyses revealed that participants with forced sex histories were 2-8 times more likely to have higher rates of mental health problems, HIV risk behavior, and substance use.

The surgical management of cephalalgia.

Purpose Of Review: Management of headache disorders is not part of most craniomaxillofacial surgery practices; however there are certain indications for surgical management of headaches by the craniomaxillofacial surgeon.

Recent Findings: Migraine headaches are the most amenable to surgical management and while the exact mechanism of migraine is unknown, a central or peripheral trigger such as compressive neuropathy of trigeminal nerve branches leading to neurogenic inflammation has been suggested. The primary management for episodic migraine headache should be lifestyle modification and medication, whereas for chronic migraine (>15 headache days/month) use of medication and botulinum neurotoxin is effective, whereas some patients may choose to explore surgical options.

Impact of EGF, IL28B, and PNPLA3 polymorphisms on the outcome of allograft hepatitis C: a multicenter study.

Hepatitis C virus (HCV) infection is accelerated following liver transplantation (LT). Single nucleotide polymorphisms (SNPs) near the epidermal growth factor (EGF) (rs4444903), IL28B (rs12979860), and PNPLA3 (rs738409) loci are associated with treatment response, fibrosis, and hepatocellular carcinoma in non-transplant hepatitis C, but allograft population data are limited. We sought to determine the role of these SNPs in 264 patients with HCV who underwent LT between 1990 and 2008.

Beyond focal cortical lesions in MS: An in vivo quantitative and spatial imaging study at 7T.

Objectives: Using quantitative T2* 7-tesla (7T) MRI as a marker of demyelination and iron loss, we investigated, in patients with relapsing-remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS), spatial and tissue intrinsic characteristics of cortical lesion(s) (CL) types, and structural integrity of perilesional normal-appearing cortical gray matter (NACGM) as a function of distance from lesions.

Methods: Patients with MS (18 RRMS, 11 SPMS), showing at least 2 CL, underwent 7T T2* imaging to obtain (1) magnitude images for segmenting focal intracortical lesion(s) (ICL) and leukocortical lesion(s) (LCL), and (2) cortical T2* maps. Anatomical scans were collected at 3T for cortical surface reconstruction using FreeSurfer.

Clergy Views on a Good Versus a Poor Death: Ministry to the Terminally Ill.

Background: Clergy are often important sources of guidance for patients and family members making medical decisions at the end-of-life (EOL). Previous research revealed spiritual support by religious communities led to more aggressive care at the EOL, particularly among minority patients. Understanding this phenomenon is important to help address disparities in EOL care.

A case of hypercalcemia secondary to hot tub lung.

Hypersensitivity pneumonitis (HP) is a diffuse granulomatous lung disease resulting from inhalation of an antigen to which an individual has been previously sensitized. Hot tub lung is an increasingly common form of HP associated with inhalation of water aerosols containing Mycobacterium avium complex organisms that contaminate hot tub water. Granulomatous lung disorders, most classically sarcoidosis, have been associated with unregulated 1-α-hydroxylase expression by macrophages present in the granulomas, causing conversion of 25-OH-vitamin D to the active form of vitamin D, 1,25(OH)2 vitamin D, and, thus, hypercalcemia.

Female resistance to pneumonia identifies lung macrophage nitric oxide synthase-3 as a therapeutic target.

To identify new approaches to enhance innate immunity to bacterial pneumonia, we investigated the natural experiment of gender differences in resistance to infections. Female and estrogen-treated male mice show greater resistance to pneumococcal pneumonia, seen as greater bacterial clearance, diminished lung inflammation, and better survival. In vitro, lung macrophages from female mice and humans show better killing of ingested bacteria.

Behavioral response inhibition in psychotic disorders: diagnostic specificity, familiality and relation to generalized cognitive deficit.

Difficulty inhibiting context-inappropriate behavior is a common deficit in psychotic disorders. The diagnostic specificity of this impairment, its familiality, and its degree of independence from the generalized cognitive deficit associated with psychotic disorders remain to be clarified. Schizophrenia, schizoaffective and bipolar patients with history of psychosis (n=523), their available first-degree biological relatives (n=656), and healthy participants (n=223) from the multi-site B-SNIP study completed a manual Stop Signal task.

Event-related potential and time-frequency endophenotypes for schizophrenia and psychotic bipolar disorder.

Background: The investigators compared event-related potential (ERP) amplitudes and event-related oscillations across a broad frequency range during an auditory oddball task using a comprehensive analysis approach to describe shared and unique neural auditory processing characteristics among healthy subjects (HP), schizophrenia probands (SZ) and their first-degree relatives, and bipolar disorder I with psychosis probands (BDP) and their first-degree relatives.

Methods: This Bipolar-Schizophrenia Network on Intermediate Phenotypes sample consisted of clinically stable SZ (n = 229) and BDP (n = 188), HP (n = 284), first-degree relatives of schizophrenia probands (n = 264), and first-degree relatives of bipolar disorder I with psychosis probands (n = 239). They were administered an auditory oddball task in the electroencephalography environment.