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Background: Diseases of the liver contribute to childhood morbidities and mortality. Early recognition and proper management of liver diseases can limit the progression to irreparable damage which requires liver transplant. However, there is scarcity of data in the pattern of liver disease in Nigerian children. Objective: To describe the pattern of paediatric liver diseases among children seen at the National Hospital, Abuja. Methods: A retrospective, descriptive study conducted at the Paediatric Gastroenterology, Hepatology and Nutrition (PGHAN) clinic and the Emergency Paediatric Unit (EPU) of National Hospital Abuja, over a 5- year period (2009 – 2014). The diagnosis of liver diseases was made from clinical and laboratory features. The data extracted from the retrieved hospital records were analyzed. Results: Forty-two out of 52 documented cases were analyzed. The children were aged 2 months to 15 years ith the mean of 7.24 ± 4.77 years. Twenty-six (62.0%) were aged >5 years (p>0.05). They comprised 31 (73.8%) males and11 (26.2%) females; 28 (66.7%) belonged to the lower socioeconomic classes while 23 (54.8%) had various forms malnutrition. Common symptoms included jaundice (30; 71.4%), abdominal pain (17; 40.5%), fever (15; 35.7%), abdominal swelling (12; 28.6%) and bleeding (8;19.0%). The signs included jaundice (30; 71.4%), hepatomegaly (16; 38.1%) and splenomegaly (8; 19.0%). Twenty-four (57.1%) had chronic viral infections while the others included neonatal hepatitis syndrome and biliary atresia (6; 14.3%), acute hepatitis (6; 14.3%) and chronic hepatitis of unidentified aetiology (4; 9.5%). Overall, the mean values of the liver enzymes and serum bilirubin were elevated while the mean values of total serum proteins and albumin levels were reduced. Five (11.9%) children improved and were discharged, 15 (35.7%) were lost to follow up with three deaths. Conclusion: Risk factors associated with liver diseases in this study included age over 5 years and lower socio-economic classes. Jaundice was the commonest clinical presentation while the most common aetiology was chronic Hepatitis B virus infection.

Local government throughout Nigeria was reconstituted on a uniform basis in 1976. The 1979 Constitution then empowered state governments to create new local governments. This article describes how the state governments have used their authority to proliferate the number of local governments; it explains the reasons for doing this both on the part of state governments and on that of local communities. The drive to create additional local governments has derived in part from a desire to promote local level development, yet enquiries into the managerial capacity of existing local governments suggest that this expectation will be frustrated. [ABSTRACT FROM AUTHOR]

Background and context: Prostate cancer is the commonest cancer affecting Nigerian men, with worse outcome compared with men from the developed world. There is limited public awareness about prostate cancer in Nigeria. Oga Blue 4 Prostate Awareness (OB4PA) was created by a consortium of Nigerian nonprofits for prostate cancer advocacy (PCA). Aims: -Design PCA using videos, printed brochure and social media -Implement PCA in five Nigerian states -Evaluate the reach and impact of PCA campaign Program/Policy process : Community-based participatory process, involving the medical community, prostate cancer survivor, and the public was used. Multimedia teaching was used to enhance learning and retention; social media was used to engage groups and individuals. Content development involved iterative consultation among project leaders, medical experts and target audience, often on social media. High-quality teaching videos were recorded in English and Nigerian Pidgin languages. Videos ensured consistency and ease of broadcast. Videos were accessed by OB4PA partners through cloud computing (OneDrive). Facebook was used to promote the campaign, engage local audience, and for Facebook Live presentation. Local health professionals projected the video in appropriate language to audiences in religious and community groups. Brochure detailing clinical features and local service providers was distributed. Audience evaluation was obtained following each interaction. Outcomes: In 6 weeks, 20 presentations were made to 1800 persons. The Facebook Live presentation had 1500 views, reached 9302 people and was shared 107 times. A total of 25 Facebook posts were made, resulting in 628 like, 1908 video views, 160 shares, and reached 14,222 people. Almost all participants had positive feedback on the free and detailed advocacy. Most questions focused on the causes and prevention of prostate cancer, especially on the use of nutritional supplements. What was learned: Cloud computing enabled us to have one presenter; this eliminated the need to find a presenter for each organization. Audience appreciated simplified videos used in explaining the disease process and need for personalized early detection. Facebook live presentation attracted the most reactions on social media, with most comments showing that people liked the intervention. Audience feedback showed that adding advocacy cellphone video by a survivor helped demystify prostate cancer. Having the main presentation video in different file formats and sizes enhanced sharing on social media, as most Nigerians access the Internet on cell phones. Reliable access to projectors was challenging, especially in remote areas. Overall, use of cloud computing and social media were crucial in the success of the PCA project. Lessons from OB4PA informed the design of the current We Can, I Can Conquer Cervical Cancer Awareness project in Nigeria. [ABSTRACT FROM AUTHOR]

The terrorist attacks on the World Trade Center (WTC) created an unprecedented environmental exposure to aerosolized dust, gases and potential carcinogens. Clonal hematopoiesis (CH) is defined as the acquisition of somatic mutations in blood cells and is associated with smoking and exposure to genotoxic stimuli. Here we show that deep targeted sequencing of blood samples identified a significantly higher proportion of WTC-exposed first responders with CH (10%; 48 out of 481) when compared with non-WTC-exposed firefighters (6.7%; 17 out of 255; odds ratio, 3.14; 95% confidence interval, 1.64-6.03; P = 0.0006) after controlling for age, sex and race/ethnicity. The frequency of somatic mutations in WTC-exposed first responders showed an age-related increase and predominantly affected DNMT3A, TET2 and other CH-associated genes. Exposure of lymphoblastoid cells to WTC particulate matter led to dysregulation of DNA replication at common fragile sites in vitro. Moreover, mice treated with WTC particulate matter developed an increased burden of mutations in hematopoietic stem and progenitor cell compartments. In summary, the high burden of CH in WTC-exposed first responders provides a rationale for enhanced screening and preventative efforts in this population., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Importance: The World Trade Center (WTC) attacks on September 11, 2001, created an unprecedented environmental exposure to known and suspected carcinogens suggested to increase the risk of multiple myeloma. Multiple myeloma is consistently preceded by the precursor states of monoclonal gammopathy of undetermined significance (MGUS) and light-chain MGUS, detectable in peripheral blood., Objective: To characterize WTC-exposed firefighters with a diagnosis of multiple myeloma and to conduct a screening study for MGUS and light-chain MGUS., Design, Setting, and Participants: Case series of multiple myeloma in firefighters diagnosed between September 11, 2001, and July 1, 2017, together with a seroprevalence study of MGUS in serum samples collected from Fire Department of the City of New York (FDNY) firefighters between December 2013 and October 2015. Participants included all WTC-exposed FDNY white, male firefighters with a confirmed physician diagnosis of multiple myeloma (n = 16) and WTC-exposed FDNY white male firefighters older than 50 years with available serum samples (n = 781)., Exposures: WTC exposure defined as rescue and/or recovery work at the WTC site between September 11, 2001, and July 25, 2002., Main Outcomes and Measures: Multiple myeloma case information, and age-adjusted and age-specific prevalence rates for overall MGUS (ie, MGUS and light-chain MGUS), MGUS, and light-chain MGUS., Results: Sixteen WTC-exposed white male firefighters received a diagnosis of multiple myeloma after September 11, 2001; median age at diagnosis was 57 years (interquartile range, 50-68 years). Serum/urine monoclonal protein isotype/free light-chain data were available for 14 cases; 7 (50%) had light-chain multiple myeloma. In a subset of 7 patients, myeloma cells were assessed for CD20 expression; 5 (71%) were CD20 positive. In the screening study, we assayed peripheral blood from 781 WTC-exposed firefighters. The age-standardized prevalence rate of MGUS and light-chain MGUS combined was 7.63 per 100 persons (95% CI, 5.45-9.81), 1.8-fold higher than rates from the Olmsted County, Minnesota, white male reference population (relative rate, 1.76; 95% CI, 1.34-2.29). The age-standardized prevalence rate of light-chain MGUS was more than 3-fold higher than in the same reference population (relative rate, 3.13; 95% CI, 1.99-4.93)., Conclusions and Relevance: Environmental exposure to the WTC disaster site is associated with myeloma precursor disease (MGUS and light-chain MGUS) and may be a risk factor for the development of multiple myeloma at an earlier age, particularly the light-chain subtype.

Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) suppress normal hematopoietic activity in part by enabling a pathogenic inflammatory milieu in the bone marrow. In this report, we show that elevation of angiopoietin-1 in myelodysplastic CD34(+) stem-like cells is associated with higher risk disease and reduced overall survival in MDS and AML patients. Increased angiopoietin-1 expression was associated with a transcriptomic signature similar to known MDS/AML stem-like cell profiles. In seeking a small-molecule inhibitor of this pathway, we discovered and validated pexmetinib (ARRY-614), an inhibitor of the angiopoietin-1 receptor Tie-2, which was also found to inhibit the proinflammatory kinase p38 MAPK (which is overactivated in MDS). Pexmetinib inhibited leukemic proliferation, prevented activation of downstream effector kinases, and abrogated the effects of TNFα on healthy hematopoietic stem cells. Notably, treatment of primary MDS specimens with this compound stimulated hematopoiesis. Our results provide preclinical proof of concept for pexmetinib as a Tie-2/p38 MAPK dual inhibitor applicable to the treatment of MDS/AML. Cancer Res; 76(16); 4841-9. ©2016 AACR., (©2016 American Association for Cancer Research.)

T cell immunity protects against diseases caused by the obligate intracellular bacterium Chlamydia trachomatis. Incidentally, host inflammatory response that includes T cells appears to also contribute to the pathogenesis of chlamydial diseases such as trachoma and tubal factor infertility (TFI). Therefore, designing effective prevention strategies requires a delineation of immune processes responsible for pathology and those mediating immunity, and identification of the immunogenetic factors predisposing to complication development. The chemokine receptor CCR5 is crucial for T cell activation and function since its deficiency causes suppression of T cell response. We investigated the hypothesis that the clearance of genital chlamydial infection in CCR5-deficient mice could be delayed in the short term; however, a beneficial effect could include protection against inflammation-related complications such as TFI. In a translational study in humans, we investigated the effect of a functional 32 bp deletion in the CCR5 gene on the risk of developing tubal pathology in Dutch Caucasian women with immunologic evidence [i.e., immunoglobulin G (IgG) responses] of chlamydial infection. When genitally-infected wild-type (WT) and CCR5 knockout (CCR5KO) mice were evaluated for microbiologic shedding of chlamydiae, there was a greater intensity of infection and delayed resolution in the knockout mice. However, compared to WT mice, the fertility of infected CCR5KO mice (measured by pregnancy rate) was only mildly affected in the short term and unaffected in the long term (70% vs 30% reduction in the short term, and 50 vs 0% in the long term, respectively). Immunobiologic analysis revealed that the diminished capacity of CCR5KO to control acute chlamydial infection correlated with the relatively low chemokine [interferon-inducible protein 10 (IP-10) and regulated upon activation normal cell expressed and secreted (RANTES)] and cytokine (mainly interferon-gamma and tumor necrosis factor-alpha) expression corresponding to a poor early T-helper I response. However, the reduced incidence of complications in the CCR5KO mice appears to correlate with the low activity of long term inflammatory mediators. Besides, the translational studies in humans revealed that among patients with positive anti-chlamydial IgG responses, tubal pathology correlated with a low incidence of CCR5delta32 deletion (7%), while women without tubal pathology had higher incidence of the CCR5delta32 deletion (31%) as compared to controls (19%). Thus, in mice and humans the inflammation associated with CCR5 function may predispose to development of complications of chlamydial infection, such as TFI.