Smoothened-dependent and -independent pathways in mammalian noncanonical Hedgehog signaling.

Hedgehog proteins are pivotal morphogens acting through a canonical pathway involving first activation of ligand binding to Patched followed by alleviation of Smoothened receptor inhibition, leading to activation of Gli transcription factors. Noncanonical Hedgehog signaling remains poorly characterized but is thought to be mainly dependent on Smoothened. However, Smoothened inhibitors have yielded only partial success in combating Hedgehog signal transduction-dependent cancer, suggesting that noncanonical Smoothened-independent pathways also are clinically relevant. Moreover, several Smoothened-dependent effects (e.g. neurite projection) do not require transcriptional activation, further suggesting biological importance of noncanonical Smoothened-dependent pathways. We comprehensively characterized the cellular kinome in Hedgehog-challenged murine WT and Smoothened-/- fibroblasts as well as Smoothened agonist-stimulated cells. A peptide assay-based kinome analysis (in which cell lysates are used to phosphorylate specific kinase substrates), along with endocytosis, Lucifer Yellow-based, and immunoblotting assays, identified an elaborate signaling network of both Smoothened-dependent and -independent pathways that mediates actin reorganization through Src-like kinases, activates various proinflammatory signaling cascades, and concomitantly stimulates Wnt and Notch signaling while suppressing bone morphogenetic protein (BMP) signaling. The contribution of noncanonical Smoothened-independent signaling to the overall effects of Hedgehog on cellular physiology appears to be much larger than previously envisioned and may explain the transcriptionally independent effects of Hedgehog signaling on cytoskeleton. The observation that Patched-dependent, Smoothened-independent, noncanonical Hedgehog signaling increases Wnt/Notch signaling provides a possible explanation for the failure of Smoothened antagonists in combating Hedgehog-dependent but Smoothened inhibitor-resistant cancer. Our findings suggest that inhibiting Hedgehog-Patched interaction could result in more effective therapies as compared with conventional Smoothened-directed therapies.

Clinical diagnostic performance evaluation of five immunoassays for antibodies to SARS-CoV-2 diagnosis in a real-life routine care setting.

While molecular techniques remain the gold standard for diagnosis of acute SARS-CoV-2 infection, serological tests have the unique potential to ascertain how much of the population has been exposed to the COVID-19 pathogen. There have been limited published studies to date documenting the performance of SARS-CoV-2 antibody assays in Nigeria and so we evaluated the diagnostic performance of five (5) immunoassay on a set of clinical samples. Five automated immunoassays (2019-nCoV IgG/IgM antibody determination kit, Tigsun COVID-19 combo IgM/IgG rapid test, rapid response COVID-19 IgG/IgM test, COVID-19 IgM-IgG combined antibody rapid test, iChroma COVID-19 Ab) were tested. Three hundred and fourteen specimens were analyzed from health care workers who tested positive PCR for SARS-CoV-2 with symptoms consistent with SARS-CoV-2 receiving treatment at two treatment centres in Nasarawa State from March to September, 2020 with control of 134 health care workers who tested negative PCR for SARS-CoV-2 with no symptoms to SARS-CoV-2. The median patients' age was 40 years (IQR 39.8-41), majority were male and were on admission. The SARS-CoV-2 IgG/IgM antibody evaluated kits had a sensitivity of 33% (2019-nCoV IgG/IgM antibody determination kit), 22% (Tigsun COVID-19 combo IgM/IgG rapid test), 43% (rapid response COVID-19 IgG/IgM test), 44% (COVID-19 IgM-IgG combined antibody rapid test), 25% (iChroma COVID-19 Ab), 100% sensitivity, accuracy of 68.5% and Kappa coefficient of 0.7 and rapid response COVID-19 IgG/IgM test cassette had a sensitivity of 33%, specificity of 100% and accuracy of 72.5% with Kappa coefficient 0.7. The Tigsun COVID-19 combo IgM/IgG rapid test (lateral flow), positive, COVID-19 IgM-IgG combined antibody rapid test and iChroma COVID-19 Ab RT all had sensitivity of zero percent. Serology was complementary to RT-PCR for the diagnosis of COVID-19 at least 14 days after onset of symptoms. The assay panel needs to be improved to serve as an option for the diagnosis of SARS-CoV-2 in resource constrained settings where there are limited molecular diagnostics testing panels.

Novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) co-infection with HIV: clinical case series analysis in North Central Nigeria.

SARS-CoV-2 has created a global public health emergency with significant mortality and morbidity for people living with HIV (PLWH). Preliminary data reveals persons with immune-compromised status are at risk of developing adverse clinical outcomes from SARS-CoV-2. We aimed to characterise clinical outcomes of HIV patients co-infected with SARS-CoV-2 infection in Nasarawa State, North Central Nigeria. We followed four (4) hospitalised HIV patients that tested positive to SARS-CoV-2 in Nasarawa State and characterised their laboratory findings and clinical outcomes. The consent of the cases was sought and they agreed that their clinical data be published. Real-time reverse transcriptase polymerase chain reaction (RT-PCR) tests for SARS-CoV-2 nucleic acid were performed using nasopharyngeal swabs (novel coronavirus PCR fluorescence diagnostic kit, BioGerm medical biotechnology) at the Nigeria Centre for Disease Control (NCDC) in Abuja, Nigeria. Our study reveals mild clinical outcome among HIV patients with SARS-CoV-2 co-infection. There is need for a syndemic framework to be used to conceptualise SARS-CoV-2 impact among HIV patients and an urgent need to strengthen healthcare programmes within Nigeria.

Person to person transmission of pneumonia associated with the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): a familial cluster analysis in North Central Nigeria.

The continued absence of viable vaccines, limited diagnostic tools, insufficient protocol for isolation period, and weak health care system in developing countries with Nigeria inclusive heightens the tension trailing the arrival of Novel SARS-CoV-2 that was officially declared a global health emergency by World Health Organization (WHO) in January 2020. In this context, this study assesses the adequacy and potency of treatment for pneumonia associated with the Novel SARS-CoV-2. Counting from 27th February 2020, exponential rise in cases of SARS-CoV-2 has been recorded in Nigeria. Despite limited data on person-to-person transmission or nosocomial transmission, we report the epidemiological features of a familial cluster of 4 positive cases to SARS-CoV-2 in Nasarawa State, North Central Nigeria. This cluster presented with an unexplained pneumonia after having contact with a family member who died after manifesting symptoms of Novel SARS-CoV-2; the test came out positive after his demise. Real-time reverse transcriptase polymerase chain reaction (RT-PCR) tests for SARS-CoV-2 nucleic acid were performed using nasopharyngeal swabs (Novel Coronavirus PCR Fluorescence Diagnostic Kit, BioGerm Medical Biotechnology at the Nigeria Centre for Disease Control (NCDC) in Abuja. Nigeria. From March 10, 2020, we enrolled a family of four patients out of a family of 10 who were positive to novel coronavirus. Four family members (aged 36-43 years) all presented with fever, upper or lower respiratory tract symptoms, or diarrhea, or a combination of these 3-6 days after exposure. These conditions continued to manifest at the Federal Medical Center, Keffi in Nasarawa State, 3-7 days after symptom onset. Their nasopharyngeal or throat swabs of these 10 family members were taken and four returned positive to coronavirus, while six tested negative. The epidemiological evidence from our study on familial cluster analysis reveals possible transmission of Novel SARS-CoV-2 during the incubation period. Study outcomes underscore the importance of probing contact history of potentially infected individuals, for prompt identification to preventing further spread.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection among health care workers in Nasarawa State, Nigeria: implications for infection prevention and control measures.

INTRODUCTION: health care workers (HCWs) are on the frontline, waging war against SARS-CoV-2 and have a higher risk of infection with exposure to an infected person with SARS-CoV-2. There is a paucity of information on clinical characteristics and infection risk gradient of HCWs with SARS-CoV-2 with the view to marshal preventive measures. METHODS: we conducted a multi-center case series analysis of 648 HCWs who were randomly selected in private and public hospitals across Nasarawa State, managing cases of SARS-CoV-2. Demographic and epidemiological information, were abstracted from electronic medical records of cases from February to July 2020. Throat and Nasopharyngeal swabs and real-time reverse transcriptase-polymerase chain reaction (RT-PCR) tests for SARS-CoV-2 nucleic acid were performed. RESULTS: overall, 134 of 648 HCWs across health centers in Nasarawa State tested positive for SARS-CoV-2. Eighty male HCWs constituted 30.9% of respondents with a median (interquartile range) age of 36.7 (30.0-47.0) years. Overall, 50 of 134 HCWs (67.5%) with SAR-COV-2 had mild disease. The five most common symptoms amongst cases were fever (67 [90.5%]), myalgia or fatigue (60 [81.1%]), cough (50[67.6%]), sore throat (50 [67.6%]), and muscle ache (50 [67.6%]). Contact with index patients (65 [59.1%]) and colleagues with infection (10 [13.9%]) as well as community-acquired infection (14 [18.9%]) were the main routes of exposure for HCWs. CONCLUSION: HCWs in Nasarawa State face an unprecedented occupational risk of morbidity and mortality as a result of SARS-CoV-2. There is need for rapid development of sustainable infection prevention control measures that protect HCWs from the SARS-CoV-2 ongoing pandemic.

Gastric cancer and Hedgehog signaling pathway: emerging new paradigms.

Ever since its initial discovery in Drosophila, hedgehog signaling has been linked to foregut development, The mammalian genome expresses three Hedgehog paralogues, sonic hedgehog (Shh), Indian Hedgehog, and desert hedgehog. In the mucosa of the embryonic and adult foregut, Shh expression is the highest. It has now become clear that hedgehog signaling is of pivotal importance in gastric homeostasis. Aberrant activation of hedgehog signaling is associated with a range of pathological consequences including various cancers. Also in gastric cancer, clinical and preclinical data support a role of Hedgehog signaling in neoplastic transformation, and gastrointestinal cancer development, also through cancer stroma interaction. Technological advance are facilitating monitoring Hedgehog signaling broadening options for the more efficient screening of individuals predisposed to eventually developing gastric cancer and targeting Hedgehog signaling may provide opportunities for prophylactic therapy once atrophic gastritis develops. Nevertheless, convincing evidence that Hedgehog antagonists are of clinically useful in the context of gastric cancer is still conspicuously lacking. Here we analyze review the role of Hedgehog in gastric physiology and the potential usefulness of targeting Hedgehog signaling in gastric cancer.

Person to person transmission of pneumonia associated with the Novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): a familial cluster analysis in North Central Nigeria

The continued absence of viable vaccines, limited diagnostic tools, insufficient protocol for isolation period, and weak health care system in developing countries with Nigeria inclusive heightens the tension trailing the arrival of Novel SARS-CoV-2 that was officially declared a global health emergency by World Health Organization (WHO) in January 2020. In this context, this study assesses the adequacy and potency of treatment for pneumonia associated with the Novel SARS-CoV-2. Counting from 27th February 2020, exponential rise in cases of SARS-CoV-2 has been recorded in Nigeria. Despite limited data on Person-to-Person transmission or nosocomial transmission, we report the epidemiological features of a familial cluster of 4 positive cases to SARS-CoV-2 in Nasarawa State, North Central Nigeria. This cluster presented with an unexplained pneumonia after having contact with a family member who died after manifesting symptoms of Novel SARS-CoV-2; the test came out positive after his demise. Real-time reverse transcriptase polymerase chain reaction (RT-PCR) tests for SARS-CoV-2 nucleic acid were performed using nasopharyngeal swabs (Novel Coronavirus PCR Fluorescence Diagnostic Kit, BioGerm Medical Biotechnology at the Nigeria Centre for Disease Control (NCDC) in Abuja. Nigeria. From March 10, 2020, we enrolled a family of four patients out of a family of 10 who were positive to novel coronavirus. Four family members (aged 36-43 years) all presented with fever, upper or lower respiratory tract symptoms, or diarrhea, or a combination of these 3-6 days after exposure. These conditions continued to manifest at the Federal Medical Center, Keffi in Nasarawa State, 3-7 days after symptom onset. Their nasopharyngeal or throat swabs of these 10 family members were taken and four returned positive to coronavirus, while six tested negative. The epidemiological evidence from our study on familial cluster analysis reveals possible transmission of Novel SARS-CoV-2 during the incubation period. Study outcomes underscore the importance of probing contact history of potentially infected individuals, for prompt identification to preventing further spread

Person to person transmission of pneumonia associated with the Novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): a familial cluster analysis in North Central Nigeria

The continued absence of viable vaccines, limited diagnostic tools, insufficient protocol for isolation period, and weak health care system in developing countries with Nigeria inclusive heightens the tension trailing the arrival of Novel SARS-CoV-2 that was officially declared a global health emergency by World Health Organization (WHO) in January 2020. In this context, this study assesses the adequacy and potency of treatment for pneumonia associated with the Novel SARS-CoV-2. Counting from 27th February 2020, exponential rise in cases of SARS-CoV-2 has been recorded in Nigeria. Despite limited data on Person-to-Person transmission or nosocomial transmission, we report the epidemiological features of a familial cluster of 4 positive cases to SARS-CoV-2 in Nasarawa State, North Central Nigeria. This cluster presented with an unexplained pneumonia after having contact with a family member who died after manifesting symptoms of Novel SARS-CoV-2; the test came out positive after his demise. Real-time reverse transcriptase polymerase chain reaction (RT-PCR) tests for SARS-CoV-2 nucleic acid were performed using nasopharyngeal swabs (Novel Coronavirus PCR Fluorescence Diagnostic Kit, BioGerm Medical Biotechnology at the Nigeria Centre for Disease Control (NCDC) in Abuja. Nigeria. From March 10, 2020, we enrolled a family of four patients out of a family of 10 who were positive to novel coronavirus. Four family members (aged 36-43 years) all presented with fever, upper or lower respiratory tract symptoms, or diarrhea, or a combination of these 3-6 days after exposure. These conditions continued to manifest at the Federal Medical Center, Keffi in Nasarawa State, 3-7 days after symptom onset. Their nasopharyngeal or throat swabs of these 10 family members were taken and four returned positive to coronavirus, while six tested negative. The epidemiological evidence from our study on familial cluster analysis reveals possible transmission of Novel SARS-CoV-2 during the incubation period. Study outcomes underscore the importance of probing contact history of potentially infected individuals, for prompt identification to preventing further spread