"Elucidating the immunomodulatory role of endocannabinoids in intervertebral disc degeneration".

Purpose: The endocannabinoid system (ECS) has been well-established to play a crucial role in the regulation of several physiological processes as well as many inflammatory disease conditions. However, its role in intervertebral disc degeneration has been least explored. We aim to investigate the immunomodulatory role of endocannabinoids in regulating IVD health.

Direct and indirect effects of hepatitis B vaccination in four low- and middle-income countries.

Population-level vaccination effects of the hepatitis B vaccine were investigated in four low- and middle-income countries with different levels of vertical and horizontal transmission. Indirect vaccination effects constitute a large proportion of overall vaccination effects of the vaccination programmes in all four countries (over 70% by 2030 in all four countries). However, countries with higher levels of vertical transmission benefit less from indirect vaccination effects from the infant hepatitis B vaccine series during the first decades of the vaccination programme, making the birth dose vaccine more important in these countries.

Diblock Copolymer Targeted Lipid Nanoparticles: Next-Generation Nucleic Acid Delivery System Produced by Confined Impinging Jet Mixers.

Despite the recent advances and clinical demonstration of lipid nanoparticles (LNPs) for therapeutic and prophylactic applications, the extrahepatic delivery of nucleic acids remains a significant challenge in the field. This limitation arises from the rapid desorption of lipid-PEG in the bloodstream and clearance to the liver, which hinders extrahepatic delivery. In response, we explore the substitution of lipid-PEG with biodegradable block copolymers (BCPs), specifically poly(ε-caprolactone)--poly(ethylene glycol) (PCL--PEG).

Identification of extracellular matrix proteins in plasma as a potential biomarker for intervertebral disc degeneration.

Purpose: Recently, there has been significant focus on extracellular matrix proteolysis due to its importance in the pathological progression of intervertebral disc degeneration (IVDD). The present study investigates the circulating levels of extracellular matrix proteins in the plasma of IVDD and determines their potential relevance as biomarkers in disc degeneration.

Methods: Global proteomic analysis was performed in the plasma samples of 10 healthy volunteers (HV) and 10 diseased subjects (DS) after depletion of highly abundant proteins such as albumin and IgG.

Proportion of pregnant women with HBV infection eligible for antiviral prophylaxis to prevent vertical transmission: A systematic review and meta-analysis.

Background & Aims: In 2020, the World Health Organization (WHO) recommended peripartum antiviral prophylaxis (PAP) for pregnant women infected with hepatitis B virus (HBV) with high viremia (≥200,000 IU/ml). Hepatitis B e antigen (HBeAg) was also recommended as an alternative when HBV DNA is unavailable. To inform policymaking and guide the implementation of prevention of mother-to-child transmission strategies, we conducted a systematic review and meta-analysis to estimate the proportion of HBV-infected pregnant women eligible for PAP at global and regional levels.

Does the gut microbiome influence disc health and disease? The interplay between dysbiosis, pathobionts, and disc inflammation: a pilot study.

Background Context: Gut microbiome alterations resulting in inflammatory responses have been implicated in many distant effects on different organs. However, its influence on disc health is still not fully investigated.

Purpose: Our objective was to document the gut biome in healthy volunteers and patients with disc degeneration and to understand the role of gut dysbiosis on human disc health.

Effectiveness of an Antibiotic-impregnated Bioabsorbable Carrier for the Treatment of Chronic Intramedullary and Diffuse Osteomyelitis.

Aim: The surgical management of chronic intramedullary osteomyelitis involves debridement of affected non-viable tissue and the use of antibiotics. Where surgery leaves a cavity, dead-space management is often through antibiotic-impregnated bone cement. These depots of local antibiotics are variable in elution properties and need removal.

Treat All versus targeted strategies to select HBV-infected people for antiviral therapy in The Gambia, west Africa: a cost-effectiveness analysis.

Background: Global elimination of hepatitis B virus (HBV) requires expanded uptake of antiviral therapy, potentially by simplifying testing algorithms, especially in resource-limited countries. We evaluated the effectiveness, cost-effectiveness, and budget impact of three strategies that determine eligibility for anti-HBV treatment, as compared with the WHO 2015 treatment eligibility criteria, in The Gambia.

Methods: We developed a microsimulation model of natural history using data from the Prevention of Liver Fibrosis and Cancer in Africa programme (known as PROLIFICA) in The Gambia, for an HBV-infected cohort of individuals aged 20 years.

Introduction to the Masterclass Series.

Harwood P, Mader K, Nayagam S. Introduction to the Masterclass Series. Strategies Trauma Limb Reconstr 2023;18(1):1.

Sequential Flash NanoPrecipitation for the scalable formulation of stable core-shell nanoparticles with core loadings up to 90.

Flash NanoPrecipitation (FNP) is a scalable, single-step process that uses rapid mixing to prepare nanoparticles with a hydrophobic core and amphiphilic stabilizing shell. Because the two steps of particle self-assembly - (1) core nucleation and growth and (2) adsorption of a stabilizing polymer onto the growing core surface - occur simultaneously during FNP, nanoparticles formulated at core loadings above approximately 70% typically exhibit poor stability or do not form at all. Additionally, a fundamental limit on the concentration of total solids that can be introduced into the FNP process has been reported previously.

Risk of early horizontal transmission of hepatitis B virus in children of uninfected mothers in sub-Saharan Africa: a systematic review and meta-analysis.

Background: Sub-Saharan Africa is highly endemic for hepatitis B virus (HBV); historically, most people were exposed during childhood through vertical or horizontal transmission. Although all African countries now provide a three-dose infant hepatitis B vaccination starting at age 6-8 weeks, only a third of African countries have introduced birth dose (HepB-BD) vaccine. Adding HepB-BD is fundamental to prevent vertical transmission, but its effectiveness in preventing horizontal transmission, compared with the three-dose infant vaccination alone, is unknown.

Global reporting of progress towards elimination of hepatitis B and hepatitis C.

Background: The 69th World Health Assembly endorsed the global health sector strategy on viral hepatitis to eliminate viral hepatitis as a public health threat by 2030. Achieving and measuring the 2030 targets requires a substantial increase in the capacity to test and treat viral hepatitis infections and a mechanism to monitor the progress of hepatitis elimination. This study aimed to identify the gaps in data availability or quality and create a new mechanism to monitor the progress of hepatitis elimination.

Cost-effectiveness of different monitoring strategies in a screening and treatment programme for hepatitis B in The Gambia.

Background: Clinical management of chronic hepatitis B virus (HBV) infection is complex and access to antiviral treatment remains limited in sub-Saharan Africa. International guidelines recommend monitoring at least annually for disease progression among HBV-infected people not meeting treatment criteria at initial diagnosis. This study aimed to assess the impact and cost-effectiveness of alternative strategies for monitoring.

Comparative metagenomic analysis of human intervertebral disc nucleus pulposus and cartilaginous end plates.

Study Design: The diversity of microflora inhabiting endplate (EP) and nucleus pulposus (NP) tissues of human intervertebral disc (IVD) was profiled through NGS-supported 16S rRNA amplicon sequencing. Sixteen EP and their corresponding NP were excised from the brain-dead voluntary organ donors with no clinical history of low back pain, and 12 herniated and 8 degenerated NP tissues isolated from the patients undergoing spinal surgery were subjected to study the alteration in the microbial diversity.

Objectives: To understand in normal IVD, whether the colonization of bacteria to the NP is through the EP in discs with intact annulus fibrosus.

Status of the HIV epidemic in Manicaland, east Zimbabwe prior to the outbreak of the COVID-19 pandemic.

Background: Manicaland province in eastern Zimbabwe has a high incidence of HIV. Completion of the seventh round of the Manicaland Survey in 2018-2019 provided the opportunity to assess the state of the epidemic prior to the start of the COVID-19 pandemic. The study aims were to: a) estimate HIV seroprevalence and assess whether prevalence has declined since the last round of the survey (2012-2013), b) describe and analyse the socio-demographic and behavioural risk factors for HIV infection and c) describe the HIV treatment cascade.

HBV continuum of care using community- and hospital-based screening interventions in Senegal: Results from the PROLIFICA programme.

Background & Aims: Strategies to implement HBV screening and treatment are critical to achieve HBV elimination but have been inadequately evaluated in sub-Saharan Africa (sSA).

Methods: We assessed the feasibility of screen-and-treat interventions in 3 real-world settings (community, workplace, and hospital) in Senegal. Adult participants were screened using a rapid HBsAg point-of-care test.

Bacteria in human lumbar discs - subclinical infection or contamination? Metabolomic evidence for colonization, multiplication, and cell-cell cross-talk of bacteria.

Background Context: The accumulating evidence associating sub-clinical infection with disc degeneration (DD) and the controversy of contamination versus infection mandates a further understanding of the microbial activity in the disc and host-microbiome interaction.

Purpose: To utilize a novel approach of metabolomics to probe the presence of bacterial metabolites involved in colonization, survival, and replication in human lumbar intervertebral discs (LIVD).

Study Design: An observational case-control study.

Novel Biomarkers of Health and Degeneration in Human Intervertebral Discs: In-depth Proteomic Analysis of Collagen Framework of Fetal, Healthy, Scoliotic, Degenerate, and Herniated Discs.

Study Design: Profiling proteins expressed in the nucleus pulposus (NP) of intervertebral discs (IVDs) in five different biological states.

Purpose: To evaluate the molecular complexity of the collagen (COL) framework and its role in the health and disease of human IVDs.

Overview Of Literature: Changes in COL composition have been linked to degenerative disk disease (DDD).

Limb reconstruction in a resource-limited environment.

Introduction: Limb salvage and reconstruction are often challenging and even more so in the limited resource setting. The purpose of this narrative review is to explore the strategies for addressing the unique obstacles and opportunities of limb reconstructive surgery in resource-limited environments globally.

Methods: We review (1) the global burden and dimension of the problem, (2) the relevance of orthopedic forums and communication, (3) free and open-access software for deformity analysis and correction, (4) bidirectional learning opportunities, and the value of fellowships and mentoring between resource-rich and resource-limited countries, and (5) how societies like SICOT can help to tackle the problem.