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Access to quality healthcare is a key requirement in every modern society. In developed countries, majority of the populace has access to quality and affordable healthcare. However, in developing countries such as Ghana, hospitals with quality infrastructure, healthcare equipment, drugs, and well-trained health practitioners are limited and expensive to access. Given the significant number of people living in extreme poverty in Ghana, it is not surprising that many people experience deterioration in their health and eventually die due to the inability to access and/or afford quality healthcare. In the current situation, where economic hardship keeps increasing in the country, there is a need to engage in a discussion on how healthcare can be made available and affordable to people of all economic classes. The purpose of this paper, therefore, is to assess the limitations that poverty places on people in their quest to access healthcare and offer solutions from theological and pastoral perspectives. This paper employed qualitative and historical descriptive research designs to describe the current state of affairs of the impact that poverty has on access to health care in Ghana. The paper used data collected from secondary sources such as books, journal articles and dissertations. After a careful analysis of the subject matter from the Ghanaian and biblical perspectives, the paper made recommendations for the nation (Ghana), the church, and all stakeholders to contribute to the provision of quality, accessible, and affordable healthcare for all irrespective of one’s financial background or economic status.

The development of e-assessment systems that can meet acceptable standards in the education industry is a present focus of researchers in the distance learning area. Cheating and impersonation in online examinations are two common challenges that have spawned diverse solutions that are usually based on continuous authentication and monitoring principles and technologies. Most of the solutions are focused on centralized e-proctoring schemes that depend massively on state-of the-art internet connectivity. However, many users of these systems, especially in the developing countries, have limited internet services. This is a major barrier to effective remote e-assessment of learners as many of these solutions fail with failing internet services. To resolve this challenge, this paper describes a Secure Offline Continuous Authentication and Monitoring(SOCAM) model for remote e-assessment.

The relevance of assessing the gingival phenotype prior to the initiation of periodontal, orthodontic, or prosthetic therapy has been clearly demonstrated. However, publications on this subject are either old or concerned with the means of assessing the gingival phenotype or the main factors likely to modify it. The main objective of this systematic review of the literature was therefore to investigate the prevalence of different gingival phenotypes in adults in good general health and with a healthy periodontium. A systematic review of the literature was performed following the guidelines of PRISMA recommendations using an electronic search strategy on four databases (PubMed, Scopus, Cochrane Library, and Embase) complemented by a manual search. Three independent authors were involved in study selection, data extraction, and bias assessment. Results: Of 807 articles, 17 of them, published between 2012 and 2023, involving 3277 subjects from 11 countries and 9766 dental sites, fulfilled the inclusion criteria. The prevalence of the gingival phenotype could not be determined at the level of an individual or a dental arch because all the publications assessed this phenotype only at the level of certain dental sectors, and were not chosen at random. The maxillary central incisors and maxillary or mandibular first molar sectors were associated with a high and thick gingival phenotype, independently of the dental morphology, gender, and age of adult subjects. Furthermore, in these regions, this gingival phenotype tended to be associated with a thick vestibular bone table. In contrast, maxillary and mandibular incisors and premolars more often had a thin gingival phenotype. For other teeth, the results were less conclusive. It is important not to rely solely on the overall appearance of the dentition but to independently assess the thickness and height of the gingiva at each dental site requiring intervention. Finally, this study highlights a key point, namely the need for further longitudinal studies to determine the prevalence in healthy adults. For practicality and feasibility reasons, these studies should be designed according to therapeutic needs, dental sector by dental sector, and within homogeneous source populations. PROSPERO registration: CRD 42023392602.

Street preaching/evangelism is one of the activities undertaken by Christians to broadcast or spread the gospel. It is one of the forms of making disciples of all nations and winning souls for Christ in accordance with the Great Commission of making disciples if all nations (Matt. 28:18-20). In Ghana and some other parts of Africa, street preaching is a common phenomenon. Arguably, street preachers have a larger audience than “pulpit preaching” at the Sunday service. While Sunday service preaching is mostly confined to the chapel and focuses on members of a particular church, street preaching targets and reaches people of varied denominational and religious backgrounds. Though a common practice, street preaching comes with a number of theological, ethical and pastoral issues which need scholarly analysis. The purpose of this paper is to critically assess street preaching from theological, ethical and pastoral perspectives and to recommend ways in which potential pitfalls may be addressed. The paper employed qualitative and historical-descriptive research designs to describe the current state of the exercise and its impact on the soul-winning ministry and Christianity in general. In addition to the data collected from the field through interviews and participant observation, the paper used secondary sources such as books, journal articles and dissertations. After a careful analysis of the subject matter the paper established that even though street preaching is a legitimate and effective way of spreading the gospel, it may contribute negatively to the qualitative growth of the church due to the lack of proper theological/ministerial training of most of these preachers and the resulting unbiblical and unethical practices that sometimes characterize this enterprise. To avert the situation, the paper made recommendations for the nation (Ghana), church and preachers to enhance the qualitative growth of the Christian community through effective and biblically-sound preaching.

The economic situation in contemporary Ghana makes everyone yearn for economic progress. In Ghana, like many other parts of Africa, religion is responsible for providing the economic, spiritual, and health needs of its adherents. The predominantly Christian population in Ghana makes many people look up to Christianity to provide the road map to the country’s success. In this regard, the prosperity theology/gospel is the most dominant approach to seeking health and wealth among Ghanaian Christians. Though very persuasive, prosperity theology prompts so much debate about its influence on the religious and socio-economic life of Christians and the society at large. On the one hand, it is considered as promoting unethical behaviour and failing to yield qualitative growth for the church. On the other hand, it is considered as attracting a large following to the Christian faith. The need to evaluate the impact of this type of teaching is an urgent theological and pastoral concern because it is the most appealing Christian approach to socio-economic breakthrough for contemporary Ghanaian Christians. This paper, therefore, sought to address the problem of the lack of a balanced assessment of the prosperity gospel and how its weaknesses can be addressed. The study is a literature-based research that gathered data from publications on the subject matter. Through a critical analysis and evaluation of the information gathered, the authors evaluated the overall impact of the prosperity theology on the holistic life (social, spiritual, economic and political) of its adherents and having noted some pitfalls, recommended how this popular theology can be refined. Apart from providing guidelines for addressing the challenges associated with the prosperity theology, the paper also has the potential of yielding ethical renewal for people to live responsibly as they work toward improving their socio-economic and spiritual lives.

Abstract This study investigated the dynamics in pyrethriod resistance and the presence/frequencies of L1014F knockdown resistance mutant allelles in Culex quinquefasciatus vector populations from Uruan Local Government Area of AkwaIbom State, Southern Nigeria between the months of March and November, 2021. Uruan LGA is among the endemic LGAs for lymphatic filariasis in AkwaIbomState. Female Anopheles mosquitoes from Eman Uruan, Ituk Mbang and Idu Uruan were exposed to permethrin, deltamethrin and alphacypermethrin in CDC insecticide coated bottles for susceptibility bioassay following standard protocols. The mosquitoes were obtained as aquatic forms from the study sites and reared under laboratory conditions to adults. The adult mosquitoes were used for this study. All the mosquitoes used for the insecticide susceptibility bioassay were morphologically identified. Standard Polymerase chain reaction (PCR) was used for authenticating the Culex quinquefasciatus species. A portion of the vgsc (917 bp) gene spanning the entire intron and the exon containing the L1014F mutation associated with knockdown resistance (kdr) in the vectorswere amplified using Allele-SPECIFIC POLYMERASE CHAIN REACTION (AS-PCR) in order to detect target site insensitivity in the vectors from the study sites. Results obtained revealed that vectors from all the study sites were resistant to permethrin insecticide (mortality rate: 18–23%). Suspected resistance (mortality rate: 90–93%) to deltamethrin and low resistance (mortality rate: 82–85%) to alphacypermethrin insecticides were detected. knockdown was more rapid with deltamethrin and alphacypermethrin than with permethrin across the study sites considering their KDT50 and KDT95. The frequency of the resistant phenotypes ranged from 35.14 to 55.3% across the study sites with a net of 45.1% resistant phenotype recorded in this study. The 1014F allelic frequency calculated from Hardy–Weinberg principle for vector populations across the study sites ranged from 0.500 (50.00%) to 0.7763 (77.63%). All populations witnessed significant (p

Teaching and learning can be effective and enjoyable if the course is well-packaged and presented. This was the experience of students and teachers participating in our hands-on Cyber Security course. Effective teaching of Cyber Security requires practical demonstration of attack patterns and their related countermeasures. This implies that outstanding and modern laboratories must be in place to teach and learn the necessary principles and practices effectively. Unfortunately, newly established universities in Sub-Saharan Africa need more funds for establishing and maintaining such laboratories. However, several researchers have shown that virtualization technology (VT) can enhance available but limited physical computing laboratories as an alternative to complex physical laboratories with huge procurement costs. This paper proposes an ad hoc and mobile laboratory for teaching practical principles in Cyber Security. The report aims to demonstrate the effectiveness of virtualization technology in teaching Cyber Security in newly established universities in Sub-Saharan Africa with zero to minimal computer laboratory infrastructure.

Abstract Onchocerciasis is a parasitic disease transmitted by black flies. Human onchocerciasis is a public health and socioeconomic problem in Nigeria. Its prevalence and morbidity have reduced over the years because of control efforts especially, Mass Drug Administration with ivermectin. The current goal is to eliminate the disease transmission by 2030. Understanding the changes in transmission patterns in Cross River State is critical to elimination of onchocerciasis in Nigeria. This study was designed to determine the transmission dynamics of onchocerciasis in Cross River State after over two decades of mass ivermectin distribution in endemic communities. Agbokim, Aningeje, Ekong Anaku and Orimekpang are four endemic communities from three Local Government Areas of the State selected for this study. Transmission indices such as infectivity rates, biting rates and transmission potentials, parity rates and diurnal biting activities were determined. A total of 15,520 adult female flies were caught on human baits, Agbokim (2831), Aningeje (6209), Ekong Anaku (4364) and Orimekpang (2116). A total of 9488 and 5695 flies were collected during the rainy and dry seasons respectively in the four communities studied. The differences in relative abundance among the communities were statistically significant (P

Generally, antimicrobial peptides (AMPs) are considered as an important part of innate immunity, due to which they provide the first line of defence against various pathogens. Additionally, they also kill pathogens that show resistance towards many antibiotics. Fishes are regularly challenged by various pathogens which not only affect their health but the risk of becoming resistant to conventional antibiotics is also increasing. As fishes shows more dependence on innate immunity, AMPs can aid as important defensive weapon in fishes. In general, AMPs exhibit various multidimensional characteristics such as neutralization of pathogens (viral, fungal & bacterial), rapidly diffuse to the infection site, and other immune cells recruitment to the infected tissues. AMPs also show various biological effects such as immunomodulation, neutralization of endotoxin and angiogenesis induction. There are numerous AMPs that have been isolated from fishes but not fully characterized at molecular level. In this review we basically focus on approaches used to design new AMP, machine learning approach, current objectives of AMPs and future prospects.

Abstract The aim of this study was the isolation and molecular characterization of fungi from untreated refinery effluent by using multiple conserved genes. The Fungi isolated were characterized based on PCR amplification and genomic sequencing of the internal transcribed spacer region (ITS), partial β-tubulin (BenA), calmodulin (CaM), and RNA polymerase second large subunit (RPB2) genes, along with morphological characterization. The obtained sequences were subjected to BLAST analysis and the corresponding fungal isolates were assigned species names after comparison with representative sequences available in GenBank. Fifteen (15) Fungi species belonging to four genera of Aspergillus, Penicillium, Fusarium, and Trichoderma with Aspergillus as the predominant genus were identified. Therefore these genes should be used as molecular markers for species level identification of fungi (especially Aspergillus and Penicillium as proven in this study.

Abstract The need for a reliable risk map in the control of soil-transmitted helminths (STHs) in Kogi East, North Central Nigeria is very important. This study was carried out to determine the effect of environmental risk factors on geospatial distribution of STHs. Epidemiological data were obtained from a district-wide survey conducted in 2018 in Kogi East. Edaphic and climatic factors were downloaded as spatial layers from international recognised health data resources centres. A total of 24 environmental factors were used in determining the risk map of STHs using MaxEnt tool. The predicted high-risk areas of A. lumbricoides, hookworms and S. stercoralis were the central part of Kogi East covering parts of Dekina, Ofu, Igalamela-Odolu, Olamaboro and Omala LGAs with probability of 0.8 to 1.00. Among the factors investigated; Temperature [mean diurnal temperature range (BIO2), temperature annual range (BIO7) and maximum temperature of the warmest month (BIO5)], precipitation [precipitation of the wettest quarter (BIO16)], and soil clay contents were the five factors that exerted most significant influence on the geospatial distribution of STHs in Kogi East, Nigeria. Public health control programmes on STHs should target high-risk areas by including them in mass drug administration, health education as well as provision of water, sanitation and hygiene infrastructures.

Abstract Background Lassa fever (LF) is a zoonotic infectious disease of public concern in Nigeria. The infection dynamics of the disease is not well elucidated in Nigeria. This study was carried out to describe the pattern of infection, case fatality rate and spread of lassa virus (LASV) from 2017 to 2020. Methods Weekly epidemiological data on LF from December, 2016 to September, 2020 were obtained from Nigeria Centre for Disease Control. The number of confirmed cases and deaths were computed according to months and states. Descriptive statistics was performed and case fatality rate was calculated. Distribution and spread maps of LF over the four years period was performed on ArcMap 10.7. Results A total of 2787 confirmed cases and 516 deaths were reported in Nigeria from December, 2016 to September, 2020. Increase in number of cases and deaths were observed with 298, 528, 796 and 1165 confirmed cases and 79, 125, 158 and 158 deaths in 2017, 2018, 2019 and 2020 respectively. Over 60% of the cases were reported in two states, Edo and Ondo states. The LF cases spread from 19 states in 2017 to 32 states and Federal Capital Territory (FCT) in 2020. Ondo state (25.39%) had the highest of deaths rate from LF over the four years. Case fatality rate (CFR) of LF was highest in 2017 (26.5%) with CFR of 23.7, 19.6 and 13.4% in 2018, 2019 and 2020 respectively. The peak of infection was in the month of February for the four years. Infections increases at the onset of dry season in November and decline till April when the wet season sets-in. Conclusion There is an annual increase in the number of LASV infection across the states in Nigeria. There is need to heighten control strategies through the use of integrated approach, ranging from vector control, health education and early diagnosis.

Abstract Background This study evaluated the effect of Jatropha curcas seed oil against adult American cockroach, Periplaneta americana, a mechanical disease vector, using three bioassay methods to determine the repellent activity, contact and fumigant toxicity. This involved the use of J. curcas oil solution (diluted with acetone (20%)) and J. curcas pure oil. For repellency test, concentrations 0.30, 0.60 and 0.90% v/v were used for the oil solution while 1.0 and 2.0 ml concentrations were used for the pure oil. All test groups were exposed for 15 min. Contact toxicity test involved the use of 0.30, 0.60, 0.90, 1.20 and 1.50% v/v concentrations for the oil solution while 1 and 2 ml concentrations were used for the pure oil. Exposure period for all test groups was 24–120 h. For the fumigant test, 0.15% v/v and 0.5 ml concentrations were used for the oil solution and pure oil groups respectively; exposure period for the test groups was 24–120 h. All test and the control groups had ten cockroaches (P. americana) per group with four replicates. Results Repellency was higher in test groups treated with pure J. curcas oil than in groups treated with the oil solution with repellency of 70–100% and 60–100% respectively after 15 min exposure period. For the contact test, a higher mortality rate was observed with the oil solution than the pure oil. Mortality was lower for 1 ml of pure oil with 20% at 24 h and 40% at 120 h than 2 ml of pure oil with 30% mortality at 24 h and 50% mortality at 120 h. A 100% mortality was recorded in the highest concentration (1.50% v/v) at 120 h. Fumigation test with 0.15% v/v of oil solution resulted in 20% mortality at 120 h while fumigation test with 0.5 ml of J. curcas pure oil resulted in 60% mortality at 120 h. Conclusion J. curcas seed oil possesses repellent and insecticidal properties against P. americana . Thus, the menace caused by this mechanical disease vector could be reduced using J. curcas seed oil.

Background: This study was conducted to determine the prevalence and risk associated with Trichomonas vaginalis amongst women in Okene metropolis, Kogi State. Methods: High vaginal swabs were collected from females of reproductive age groups using swab sticks from February to May 2019 and were examined microscopically using wet mount preparation and were confirmed with Dorset culture method. Structured questionnaires were administered to assess the risk factors. Results: A total of 180 (40.7%) women were infected with T. vaginalis. The General Hospital had the highest prevalence of 80 women (42.1%), whereas the least was from Oyiza Hospital (66 women, 39.3%). The age group of 21–30 years (65, 55.1%) had the highest prevalence, whereas the age group of 14–20 years (20, 25.0%) had the least prevalence. Divorced women, women with multiple partners and those that do not use condom are at higher risk of infections. Conclusion: T. vaginalis is endemic amongst women in Okene metropolis, Kogi State, with an overall prevalence of 40.7%. Proper awareness on this disease should be heightened to help reduce the burden of infection.

The negative impact of soil-transmitted helminths (STHs) in Nigeria is enormous, and it poses serious public health issues and concerns. This study was undertaken to investigate the impact of health education intervention on reinfection of STHs in pupils of rural schools of Kogi East, North Central Nigeria. A total of 10 schools with the highest prevalence of STHs at baseline were selected from the 45 schools assessed during the baseline survey. These 10 schools were randomly paired into two groups of 5 schools per group. Five schools were dewormed and given health education (DHE) intervention while the other 5 schools were dewormed only (DO) without health education. Reassessment of schools for reinfection was carried out for a period of 12 months. Data obtained were analyzed using descriptive statistics. Student’s t-test was used to make comparison between interventions in the incidence of infections. Analysis was carried out at p0.05). School-based health education intervention had no significant impact on STH incidence in pupils of rural schools in Kogi East. Community-based deworming should be encouraged alongside improvement in the water, sanitation, and hygiene infrastructures and practices at both school and home.

There is a need to find better and safer remedy for ulcerative colitis (UC) than available drugs to stem the rising incidence of the disease. This study assessed the anti-ulcerative colitis efficacy of Cassia tora (CT) leaf, a safe medicinal plant used to treat many diseases including but not limited to ulcer, dyspepsia, gastritis and colitis. Twenty adult male BALB/c mice were divided into four groups of 5 mice each. Group 1 was the control; groups 2 through 4 were exposed to 3% dextran sulfate sodium (DSS) via drinking water for 5 days to induce UC. Mice in groups 3 and 4 were then administered with 400 mg/kg of CT and 50 mg/kg of azathioprine, respectively, for 14 days, while group 2 was non-treated. The mice were afterward sacrificed for gross pathological, histopathological, and biochemical examinations. Compared with non-treated, CT and azathioprine significantly (p≤0.05) reversed pathologies associated with UC such as diarrhea and bleeding, loss of body weight, shortening of colon, increased colon weight/length ratio, and increased disease activity index (DAI) score. Histopathological examination showed that CT and azathioprine restored damaged colon tissues of the UC-induced mice compared with non-treated. Similar trends were also observed in the biochemical examination as mice treated with CT and azathioprine significantly reduced malondialdehyde (MDA) levels and increased the superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT) activity compared with non-treated. In all health indices evaluated, CT performed better than azathioprine. It can be inferred from the results that CT possesses potent anti-ulcerative colitis properties.

The aim of this study was to evaluate the removal of Pb (II) and Ni (II) from untreated waste water using sugarcane bagasse and possible desorption of the metal ions from the adsorbent for effective re-use. The effects of pH (4-6), temperature (30−70 °C), contact time (30−150 min) and adsorbent dosage (0.3−0.7 g) were examined. Optimum conditions for the removal efficiencies of Pb (89.31 %) and Ni (96.33 %) were pH, 6.0; temperature, 30 °C; contact time, 90 min. and adsorbent dosage, 0.5 g. The maximum monolayer adsorption capacities of Pb (II) and Ni (II) were 1.61 mg/g and 123.46 mg/g respectively, by fitting the equilibrium data to the Langmuir isotherm model. Freundlich isotherm and pseudo second order kinetic models were best fitted for Pb (II) and Ni (II) uptake. Desorption of the metal ions from the metal-loaded bagasse was best performed by HNO3 with removal efficiency of 85.2 %. Therefore, sugarcane bagasse has a high potential for removal of heavy metals from waste water and can be re-used at any time after desorption without losing its efficiency.

Freshwater fish species are posing health challenges by either serving as host of parasites that are harmful to man and animals. This study was conducted to determine the parasitic profile of the branchial and gastrointestinal tracts of freshwater fish species from Niger and Benue rivers at Lokoja. These fish species are Tilapia zillii, Oreochromis niloticus, Clarias species, Synodontis schall, and Megalops atlanticus. Fish samples were collected within a period of 12 months, and the species and sex of the fish were identified. The two opercula of each fish were removed and examined for parasites; parasites recovered were preserved in 0.7% physiological saline. Gastrointestinal tracts were removed from each fish, placed in physiological saline, and examined microscopically for parasites. Prevalence of parasites was calculated. The chi-square test was used to compare prevalence of parasites according to sexes, body parts examined, fish species, and parasites species, while the t-test was used to compare between gills and intestines of each fish species. The chi-square test was used to determine if any significant difference exists in prevalence between the sexes, body parts, fish species, and parasites species, while the t-test was used to determine if any significant difference exists in prevalence between the gills and intestines of each fish species. A total of seven parasites species were harboured in branchial chamber and gastrointestinal tracts of fish species from rivers Niger and Benue: Clinostomum sp. (trematode), Camallanus sp. (nematode), Capillaria sp., Rhabdochona congolensis (nematode), Contracaecum sp. (nematode), Proteocephalus sp. (cestode), and Spinitectus guntheri. T. zillii (81 (95.3%)) had the highest prevalence, while O. niloticus, Clarias sp., S. schall, and M. atlanticus had prevalence of 87 (89.7%), 96 (80.0%), 48 (70.6%), and 27 (38.6%), respectively. Out of the total fish samples examined, females (191 (80.3%)) were observed to harbour more parasites than males (148 (73.3%)). The gastrointestinal tracts (287 (65.2%)) significantly harboured more parasites than branchial chamber (52 (11.8%)). Fish species in rivers Niger and Benue are highly infected with parasites. Fish consumers should subject the fish to proper processing before consumption, as some of these parasites are of zoonotic importance.

Schistosomiasis and soil-transmitted helminthiasis (STH) are neglected tropical diseases (NTDs) that cause chronic infections and ill health. The study was carried out to determine the current infection status and risk factors associated with Schistosoma haematobium and soil-transmitted helminth (STH) coinfection among school children in Biase Local Government Area (LGA), Cross River State, Nigeria. A cross-sectional study was carried out. Urine and fecal samples were randomly collected from 630 school children in six villages of Biase LGA. Urine sedimentation and Kato-Katz techniques were used to diagnose urogenital schistosomiasis and STHs, respectively. A structured questionnaire was used to collect demographic information and risk factors. The prevalence of S. haematobium in Biase LGA was 6.03%, with males (27 pupils, 9.00%) significantly more (χ2=8.903, p value = 0.003, C.I.=−82.650–120.650) infected than the females (11 pupils, 3.33%), while the prevalence of STH infection was 11.27% with no significant difference (χ2=0.002, p value = 0.962, C.I.=−16.441–54.559) in prevalence between males (34 pupils, 11.33%) and females (37 pupils, 11.21%). Prevalence of S. haematobium and STHs ranged from 1.82 to 19.13% and from 4.55 to 19.05% within the communities, respectively, with Abini (22 pupils, 19.13%) and Adim (20 pupils, 19.05%) communities having the highest prevalence for S. haematobium and STHs, respectively. The most infected age group was 11–13 years (21 pupils, 9.68%) for S. haematobium and 14–16 years (5 pupils, 21.74%) for STHs. Ascaris lumbricoides, hookworms, and Trichuris trichiura had prevalence of 5.56%, 3.02%, and 2.70%, respectively. An overall prevalence of 7.14% and 8.41% was observed for haematuria and proteinuria, respectively. Prevalence of coinfection among the parasites was 4.76%. Male pupils (OR=2.868, C.I.: 1.397–5.889), pupils of the age group of 11–13 years (OR=2.496, C.I.: 1.287–4.838), school children that swim (OR=1.527, C.I.: 0.784–2.974), those that cross streams to farm (OR=25.286, C.I.: 4.091–156.283), those that visit stream or river severally (OR=3.077, C.I.: 1.204–7.863), and those whose home is 1 km (OR=3.116, C.I.: 1.292–7.518) from the stream are at higher odds of infection with S. haematobium. For STHs, male pupils (OR=1.012, C.I.: 0.617–1.659), pupils of the age group of 11–13 years (OR=2.609, C.I.: 1.582–4.302), pupils that walk barefoot (OR=18.746, C.I.: 6.786–51.783), those that do not wash fruits and vegetables before eating (OR=2.334, C.I.: 1.400–3.892), those that do not wash hands after using the toilet (OR=1.200, C.I.: 0.730–1.973), those that eat soils (OR=2.741, C.I.: 1.533–4.902), those that drink water from streams or rivers (OR=189.509, C.I.: 24.807–1447.740), and those that use pit latrine (OR=2.920, C.I.: 1.746–4.885) and/or open defecation (OR=2.552, C.I.: 1.454–4.479) are at high odds of being infected with STHs. Urogenital schistosomiasis and soil-transmitted helminthiasis are still endemic diseases in Biase LGA. Although the degree of infection is quite low or moderate, there is a need to intensify and sustain control measures such as provision of sustainable clean water supply, health education intervention, and chemotherapy.

This study was undertaken to investigate the status of Soil-transmitted Helminths (STHs) in rural schools of Kogi East, Nigeria. The study was cross-sectional using stratified random cluster sampling procedure. Stool specimens were collected in a sterile specimen bottle from school pupils in five (5) randomly selected schools in each of the nine Local Government Areas (LGAs) (45 schools) of Kogi East to enable complete epidemiological survey, all schools selected were located within the rural areas of the LGAs. Collected samples were preserved in 10% formalin and examined for parasites using formal ether sedimentation technique. Structured questionnaires were administered to obtain information on the risk factors associated with STHs. Data were analysed using descriptive statistics and Chi-square test was used to test the relationship in prevalence of STHs according to categories of infections. The overall prevalence of STHs in Kogi East was 17.1% with Ascaris lumbricoides, hookworms and Strongyloides stercoralis having prevalence of 4.3%, 12.7% and 1.1% respectively. Hookworms’ infection was the most widespread in Kogi East. Omala LGA (29.6%) had the highest prevalence of STHs. No significant difference (p > 0.05) in prevalence between male (18.2%) and female (16.0%) pupils, and between the age groups of 5–8 years (16.6%) and 9–12 years (17.8%). STHs is endemic among rural pupils of Kogi East as observed in the prevalence of infection as well as the prevailing risk factors, preventive chemotherapy is warranted. Therefore, school-based deworming alongside health education programme should be extended to rural schools.

Abstract Background In low and middle-income countries, such as Ghana, communication disability is poorly recognised and rehabilitation services for people with communication disability are limited. As rehabilitation services for communication disability develop, and the profession of speech-language pathology grows, it is important to consider how services can most appropriately respond to the needs and preferences of the community. Understanding the ways in which people currently self-help and seek help for communication disability is central to developing services that build on existing local practices and are relevant to the community. Methods A qualitative descriptive survey was used to explore likely self-help and help-seeking behaviours for communication disability, in Accra, Ghana. The survey required participants to describe responses to hypothetical scenarios related to communication disability. A mix of theoretical sampling and convenience sampling was used. Qualitative content analysis was used to analyse data and develop categories and subcategories of reported self-help behaviours and sources of help and advice for communication disability. Results One hundred and thirty-six participants completed the survey. Results indicated that community members would be likely to engage in a variety self-help strategies in response to communication disability. These included working directly with a person with a communication disability to attempt to remediate a communication impairment, altering physical and communication environments, changing attitudes or care practices, educating themselves about the communication disability, providing resources, and responding in spiritual ways. Participants indicated that they would seek help for communication disability across a range of sectors – including the Western healthcare, religious, and traditional sectors. Conclusions Understanding existing community actions to self-help and help-seek may allow emerging communication rehabilitation services, including the profession of speech-language pathology, to build on existing community practices in resource-limited contexts such as Ghana.

The living coelacanth Latimeria (Sarcopterygii: Actinistia) is an iconic, so-called 'living fossil' within one of the most apparently morphologically conservative vertebrate groups. We describe a new, 3-D preserved coelacanth from the Late Devonian Gogo Formation in Western Australia. We assemble a comprehensive analysis of the group to assess the phylogeny, evolutionary rates, and morphological disparity of all coelacanths. We reveal a major shift in morphological disparity between Devonian and post-Devonian coelacanths. The newly described fossil fish fills a critical transitional stage in coelacanth disparity and evolution. Since the mid-Cretaceous, discrete character changes (representing major morphological innovations) have essentially ceased, while meristic and continuous characters have continued to evolve within coelacanths. Considering a range of putative environmental drivers, tectonic activity best explains variation in the rates of coelacanth evolution., (© 2024. The Author(s).)

Accumulation of misfolded proteins or perturbation of calcium homeostasis leads to endoplasmic reticulum (ER) stress and is linked to the pathogenesis of neurodegenerative diseases. Hence, understanding the ability of neuronal cells to cope with chronic ER stress is of fundamental interest. Interestingly, several brain areas uphold functions that enable them to resist challenges associated with neurodegeneration. Here, we established novel clonal mouse hippocampal (HT22) cell lines that are resistant to prolonged (chronic) ER stress induced by thapsigargin (TgR) or tunicamycin (TmR) as in vitro models to study the adaption to ER stress. Morphologically, we observed a significant increase in vesicular und autophagosomal structures in both resistant lines and 'giant lysosomes', especially striking in TgR cells. While autophagic activity increased under ER stress, lysosomal function appeared slightly impaired; in both cell lines, we observed enhanced ER-phagy. However, proteomic analyses revealed that various protein clusters and signaling pathways were differentially regulated in TgR versus TmR cells in response to chronic ER stress. Additionally, bioenergetic analyses in both resistant cell lines showed a shift toward aerobic glycolysis ('Warburg effect') and a defective complex I of the oxidative phosphorylation (OXPHOS) machinery. Furthermore, ER stress-resistant cells differentially activated the unfolded protein response (UPR) comprising IRE1α and ATF6 pathways. These findings display the wide portfolio of adaptive responses of neuronal cells to chronic ER stress. ER stress-resistant neuronal cells could be the basis to uncover molecular modulators of adaptation, resistance, and neuroprotection as potential pharmacological targets for preventing neurodegeneration., Competing Interests: Declaration of competing interest There is no conflict of interest of all authors regarding the manuscript “Adaptive responses of neuronal cells to chronic endoplasmic reticulum (ER) stress”., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Jensen et al . ( 1 ) question evidence presented of a chambered heart within placoderms, citing its small size and apparently ventral atrium. However, they fail to note the belly-up orientation of the placoderm within one nodule, and the variability of heart morphology within extant taxa. Thus, we remain confident in our interpretation of the mineralized organ as the heart.

Access to commercial CD19 CAR-T cells remains limited even in wealthy countries like Canada due to clinical, logistical, and financial barriers related to centrally manufactured products. We created a non-commercial academic platform for end-to-end manufacturing of CAR-T cells within Canada's publicly funded healthcare system. We report initial results from a single-arm, open-label study to determine the safety and efficacy of in-house manufactured CD19 CAR-T cells (entitled CLIC-1901) in participants with relapsed/refractory CD19 positive hematologic malignancies. Using a GMP compliant semi-automated, closed process on the Miltenyi Prodigy, T cells were transduced with lentiviral vector bearing a 4-1BB anti-CD19 CAR transgene and expanded. Participants underwent lymphodepletion with fludarabine and cyclophosphamide, followed by infusion of non-cryopreserved CAR-T cells. Thirty participants with non-Hodgkin's lymphoma (n=25) or acute lymphoblastic leukemia (n=5) were infused with CLIC-1901: 21 males (70%), median age 66 (range 18-75). Time from enrollment to CLIC-1901 infusion was a median of 20 days (range 15-48). The median CLIC-1901 dose infused was 2.3 × 10 6 CAR-T cells/kg (range 0.13-3.6 × 10 6 /kg). Toxicity included ≥ grade 3 cytokine release syndrome (n=2) and neurotoxicity (n=1). Median follow-up was 6.5 months. Overall response rate at day 28 was 76.7%. Median progression-free and overall survival was 6 months (95%CI 3-not estimable) and 11 months (95% 6.6-not estimable), respectively. This is the first trial of in-house manufactured CAR-T cells in Canada and demonstrates that administering fresh CLIC-1901 product is fast, safe, and efficacious. Our experience may provide helpful guidance for other jurisdictions seeking to create feasible and sustainable CAR-T cell programs in research-oriented yet resource-constrained settings., Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT03765177, identifier NCT03765177., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kekre, Hay, Webb, Mallick, Balasundaram, Sigrist, Clement, Nielsen, Quizi, Yung, Brown, Dreolini, Waller, Smazynski, Gierc, Loveless, Clark, Dyer, Hogg, McCormick, Gignac, Bell, Chapman, Bond, Yong, Fung, Lockyer, Hodgson, Murphy, Subramanian, Wiebe, Yoganathan, Medynski, Vaillan, Black, McDiarmid, Kennah, Hamelin, Song, Narayanan, Rodrigo, Dupont, Hawrysh, Presseau, Thavorn, Lalu, Fergusson, Bell, Atkins, Nelson and Holt.)

The origin and early diversification of jawed vertebrates involved major changes to skeletal and soft anatomy. Skeletal transformations can be examined directly by studying fossil stem gnathostomes; however, preservation of soft anatomy is rare. We describe the only known example of a three-dimensionally mineralized heart, thick-walled stomach, and bilobed liver from arthrodire placoderms, stem gnathostomes from the Late Devonian Gogo Formation in Western Australia. The application of synchrotron and neutron microtomography to this material shows evidence of a flat S-shaped heart, which is well separated from the liver and other abdominal organs, and the absence of lungs. Arthrodires thus show the earliest phylogenetic evidence for repositioning of the gnathostome heart associated with the evolution of the complex neck region in jawed vertebrates.

Background: Recent calls to action have been made for Implementation Science to attend to health inequities at the intersections of race, gender, and social injustice in the United States. Transgender people, particularly Black and Latina transgender women, experience a range of health inequities and social injustices. In this study, we compared two processes of transgender community engagement in Los Angeles and in Chicago as an implementation strategy to address inequitable access to care; we adapted and extended the Exploration Planning Implementation and Sustainment (EPIS) framework for transgender health equity., Methods: A comparative case method and the EPIS framework were used to examine parallel implementation strategies of transgender community engagement to expand access to care. To foster conceptual development and adaptation of EPIS for trans health equity, the comparative case method required detailed description, exploration, and analyses of the community-engagement processes that led to different interventions to expand access. In both cities, the unit of analysis was a steering committee made up of local transgender and cisgender stakeholders., Results: Both steering committees initiated their exploration processes with World Café-style, transgender community-engaged events in order to assess community needs and structural barriers to healthcare. The steering committees curated activities that amplified the voices of transgender community members among stakeholders, encouraging more effective and collaborative ways to advance transgender health equity. Based on analysis and findings from the Los Angeles town hall, the steering committee worked with a local medical school, extending the transgender medicine curriculum, and incorporating elements of transgender community-engagement. The Chicago steering committee determined from their findings that the most impactful intervention on structural racism and barriers to healthcare access would be to design and pilot an employment program for Black and Latina transgender women., Conclusion: In Los Angeles and Chicago, transgender community engagement guided implementation processes and led to critical insights regarding specific, local barriers to healthcare. The steering committee itself represented an important vehicle for individual-, organizational-, and community-level relationship and capacity building. This comparative case study highlights key adaptations of EPIS toward the formation of an implementation science framework for transgender health equity., (© 2022. The Author(s).)

The lobe-finned fish, lungfish (Dipnoi, Sarcoptergii), have persisted for ~400 million years from the Devonian Period to present day. The evolution of their dermal skull and dentition is relatively well understood, but this is not the case for the central nervous system. While the brain has poor preservation potential and is not currently known in any fossil lungfish, substantial indirect information about it and associated structures (e.g. labyrinths) can be obtained from the cranial endocast. However, before the recent development of X-ray tomography as a palaeontological tool, these endocasts could not be studied non-destructively, and few detailed studies were undertaken. Here, we describe and illustrate the endocasts of six Palaeozoic lungfish from tomographic scans. We combine these with six previously described digital lungfish endocasts (4 fossil and 2 recent taxa) into a 12-taxon dataset for multivariate morphometric analysis using 17 variables. We find that the olfactory region is more highly plastic than the hindbrain, and undergoes significant elongation in several taxa. Further, while the semicircular canals covary as an integrated module, the utriculus and sacculus vary independently of each other. Functional interpretation suggests that olfaction has remained a dominant sense throughout lungfish evolution, and changes in the labyrinth may potentially reflect a change from nektonic to near-shore environmental niches. Phylogenetic implications show that endocranial form fails to support monophyly of the 'chirodipterids'. Those with elongated crania similarly fail to form a distinct clade, suggesting these two paraphyletic groups have converged towards either head elongation or truncation driven by non-phylogenetic constraints., Competing Interests: AC, TC, RC, LH, PA, SC, JL No competing interests declared, (© 2022, Clement et al.)

Human papillomaviruses (HPVs) inflict a significant burden on the human population. The clinical manifestations caused by high-risk HPV types are cancers at anogenital sites, including cervical cancer, as well as head and neck cancers. Host cell defense mechanisms such as autophagy are initiated upon HPV entry. At the same time, the virus modulates cellular antiviral processes and structures such as promyelocytic leukemia nuclear bodies (PML NBs) to enable infection. Here, we uncover the autophagy adaptor p62, also known as p62/sequestosome-1, as a novel proviral factor in infections by the high-risk HPV type 16 (HPV16). Proteomics, imaging and interaction studies of HPV16 pseudovirus-treated HeLa cells display that p62 is recruited to virus-filled endosomes, interacts with incoming capsids, and accompanies the virus to PML NBs, the sites of viral transcription and replication. Cellular depletion of p62 significantly decreased the delivery of HPV16 viral DNA to PML NBs and HPV16 infection rate. Moreover, the absence of p62 leads to an increase in the targeting of viral components to autophagic structures and enhanced degradation of the viral capsid protein L2. The proviral role of p62 and formation of virus-p62-PML hybrid bodies have also been observed in human primary keratinocytes, the HPV target cells. Together, these findings suggest the previously unrecognized virus-induced formation of p62-PML hybrid bodies as a viral mechanism to subvert the cellular antiviral defense, thus enabling viral gene expression.

Background: Primary sclerosing cholangitis (PSC) is an indication for liver transplantation, but recurrence after liver transplantation is associated with poor outcomes often requiring repeat transplantation. We investigated whether autologous hematopoietic stem cell transplantation (aHSCT) could be used to stop progression of recurrent PSC and promote operational tolerance., Methods: Twelve patients with recurrent PSC were fully evaluated and 5 were selected for aHSCT. Autologous hematopoietic stem cells were collected, purified by CD34 immunomagnetic selection, and cryopreserved. Immunoablation using busulfan, cyclophosphamide, and rabbit antithymocyte globulin was followed by aHSCT. The primary endpoint of the study was the establishment of operational tolerance defined as lack of biochemical, histologic, and clinical evidence of rejection while off immunosuppression at 2 y post-aHSCT., Results: Two of the 5 patients achieved operational tolerance with no clinical or histologic evidence of PSC progression or allorejection. A third patient developed sinusoidal obstruction syndrome following aHSCT requiring repeat liver transplantation but has no evidence of PSC recurrence while on sirolimus monotherapy now >3 y after aHSCT. A fourth patient was weaned off immunosuppression but died 212 d after aHSCT from pericardial constriction. A fifth patient died from multiorgan failure. Immunosuppression-free allograft acceptance was associated with deletion of T-cell clones, loss of autoantibodies, and increases in regulatory T cells, transitional B cells, and programmed cell death protein-1 expressing CD8+ T cells in the 2 long-term survivors., Conclusions: Although operational tolerance occurred following aHSCT, the high morbidity and mortality observed render this specific protocol unsuitable for clinical adoption., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The megalichthyids are one of several clades of extinct tetrapodomorph fish that lived throughout the Devonian-Permian periods. They are advanced "osteolepidid-grade" fishes that lived in freshwater swamp and lake environments, with some taxa growing to very large sizes. They bear cosmine-covered bones and a large premaxillary tusk that lies lingually to a row of small teeth. Diagnosis of the family remains controversial with various authors revising it several times in recent works. There are fewer than 10 genera known globally, and only one member definitively identified from Gondwana. Cladarosymblema narrienense Fox et al. 1995 was described from the Lower Carboniferous Raymond Formation in Queensland, Australia, on the basis of several well-preserved specimens. Despite this detailed work, several aspects of its anatomy remain undescribed., Methods: Two especially well-preserved 3D fossils of Cladarosymblema narrienense , including the holotype specimen, are scanned using synchrotron or micro-computed tomography (µCT), and 3D modelled using specialist segmentation and visualisation software. New anatomical detail, in particular internal anatomy, is revealed for the first time in this taxon. A novel phylogenetic matrix, adapted from other recent work on tetrapodomorphs, is used to clarify the interrelationships of the megalichthyids and confirm the phylogenetic position of C. narrienense ., Results: Never before seen morphological details of the palate, hyoid arch, basibranchial skeleton, pectoral girdle and axial skeleton are revealed and described. Several additional features are confirmed or updated from the original description. Moreover, the first full, virtual cranial endocast of any tetrapodomorph fish is presented and described, giving insight into the early neural adaptations in this group. Phylogenetic analysis confirms the monophyly of the Megalichthyidae with seven genera included ( Askerichthys, Cladarosymblema, Ectosteorhachis, Mahalalepis, Megalichthys, Palatinichthys, and Sengoerichthys ). The position of the megalichthyids as sister group to canowindrids, crownward of "osteolepidids" (e.g., Osteolepis and Gogonasus ), but below "tristichopterids" such as Eusthenopteron is confirmed, but our findings suggest further work is required to resolve megalichthyid interrelationships., Competing Interests: The authors declare there are no competing interests., (©2021 Clement et al.)

Nondegradative ubiquitin chains attached to specific targets via Lysine 63 (K63) residues have emerged to play a fundamental role in synaptic function. The K63-specific deubiquitinase CYLD has been widely studied in immune cells and lately also in neurons. To better understand if CYLD plays a role in brain and synapse homeostasis, we analyzed the behavioral profile of CYLD-deficient mice. We found that the loss of CYLD results in major autism-like phenotypes including impaired social communication, increased repetitive behavior, and cognitive dysfunction. Furthermore, the absence of CYLD leads to a reduction in hippocampal network excitability, long-term potentiation, and pyramidal neuron spine numbers. By providing evidence that CYLD can modulate mechanistic target of rapamycin (mTOR) signaling and autophagy at the synapse, we propose that synaptic K63-linked ubiquitination processes could be fundamental in understanding the pathomechanisms underlying autism spectrum disorder., Competing Interests: The authors declare no competing interest.

The production of blood cells (haematopoiesis) occurs in the limb bones of most tetrapods but is absent in the fin bones of ray-finned fish. When did long bones start producing blood cells? Recent hypotheses suggested that haematopoiesis migrated into long bones prior to the water-to-land transition and protected newly-produced blood cells from harsher environmental conditions. However, little fossil evidence to support these hypotheses has been provided so far. Observations of the humeral microarchitecture of stem-tetrapods, batrachians, and amniotes were performed using classical sectioning and three-dimensional synchrotron virtual histology. They show that Permian tetrapods seem to be among the first to exhibit a centralised marrow organisation, which allows haematopoiesis as in extant amniotes. Not only does our study demonstrate that long-bone haematopoiesis was probably not an exaptation to the water-to-land transition but it sheds light on the early evolution of limb-bone development and the sequence of bone-marrow functional acquisitions., Competing Interests: JE, PT, AC, JK, GN, CB, SS No competing interests declared, (© 2021, Estefa et al.)

The cellular protein homeostasis (proteostasis) network responds effectively to insults. In a functional screen in C. elegans, we recently identified the gene receptor-mediated endocytosis 8 (rme-8; human ortholog: DNAJC13) as a component of the proteostasis network. Accumulation of aggregation-prone proteins, such as amyloid-β 42 (Aβ), α-synuclein, or mutant Cu/Zn-superoxide dismutase (SOD1), were aggravated upon the knockdown of rme-8/DNAJC13 in C. elegans and in human cell lines, respectively. DNAJC13 is involved in endosomal protein trafficking and associated with the retromer and the WASH complex. As both complexes have been linked to autophagy, we investigated the role of DNAJC13 in this degradative pathway. In knockdown and overexpression experiments, DNAJC13 acts as a positive modulator of autophagy. In contrast, the overexpression of the Parkinson's disease-associated mutant DNAJC13(N855S) did not enhance autophagy. Reduced DNAJC13 levels affected ATG9A localization at and its transport from the recycling endosome. As a consequence, ATG9A co-localization at LC3B-positive puncta under steady-state and autophagy-induced conditions is impaired. These data demonstrate a novel function of RME-8/DNAJC13 in cellular homeostasis by modulating ATG9A trafficking and autophagy.

The transition from water to land by the earliest tetrapods in the Devonian Period is seen as one of the greatest steps in evolution. However, little is understood concerning changes in brain morphology over this transition. Here, we determine the brain-braincase relationship in fishes and basal lissamphibians as a proxy to elucidate the changes that occurred over the fish-tetrapod transition. We investigate six basal extant sarcopterygians spanning coelacanths to salamanders ( Latimeria chalumnae, Neoceratodus, Protopterus aethiopicus, P. dolloi, Cynops, Ambystoma mexicanum ) using micro-CT and MRI and quantify the brain-braincase relationship in these extant taxa. Our results show that regions of lowest brain-endocast disparity are associated with regions of bony reinforcement directly adjacent to masticatory musculature for the mandible except in Neoceratodus and Latimeria . In Latimeria this deviation from the trend can be accounted for by the possession of an intracranial joint and basicranial muscles, whereas in Neoceratodus difference is attributed to dermal bones contributing to the overall neurocranial reinforcement. Besides Neoceratodus and Latimeria, regions of low brain-endocast disparity occur where there is less reinforcement away from high mandibular muscle mass, where the trigeminal nerve complex exits the braincase and where endolymphatic sacs occupy space between the brain and braincase wall. Despite basal tetrapods possessing reduced adductor muscle mass and a different biting mechanism to piscine sarcopterygians, regions of the neurocranium lacking osteological reinforcement in the basal tetrapods Lethiscus and Brachydectes broadly correspond to regions of high brain-endocast disparity seen in extant taxa., Competing Interests: The authors declare no competing financial or non-financial interests., (© 2020 The Authors.)

The evolution of fishes to tetrapods (four-limbed vertebrates) was one of the most important transformations in vertebrate evolution. Hypotheses of tetrapod origins rely heavily on the anatomy of a few tetrapod-like fish fossils from the Middle and Late Devonian period (393-359 million years ago) 1 . These taxa-known as elpistostegalians-include Panderichthys 2 , Elpistostege 3,4 and Tiktaalik 1,5 , none of which has yet revealed the complete skeletal anatomy of the pectoral fin. Here we report a 1.57-metre-long articulated specimen of Elpistostege watsoni from the Upper Devonian period of Canada, which represents-to our knowledge-the most complete elpistostegalian yet found. High-energy computed tomography reveals that the skeleton of the pectoral fin has four proximodistal rows of radials (two of which include branched carpals) as well as two distal rows that are organized as digits and putative digits. Despite this skeletal pattern (which represents the most tetrapod-like arrangement of bones found in a pectoral fin to date), the fin retains lepidotrichia (fin rays) distal to the radials. We suggest that the vertebrate hand arose primarily from a skeletal pattern buried within the fairly typical aquatic pectoral fin of elpistostegalians. Elpistostege is potentially the sister taxon of all other tetrapods, and its appendages further blur the line between fish and land vertebrates.

Neurodegenerative diseases are linked to dysfunctional proteostasis and disturbed autophagy. Here, we discuss how the sigma-1 receptor (Sig-1R) may act at the intersection of this interaction, as loss-of-function mutations of this unique chaperone are associated with defective autophagy and its pharmacological activation induces autophagic activity., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Palaeognathae is a basal clade within Aves and include the large and flightless ratites and the smaller, volant tinamous. Although much research has been conducted on various aspects of palaeognath morphology, ecology, and evolutionary history, there are still areas which require investigation. This study aimed to fill gaps in our knowledge of the Southern Cassowary, Casuarius casuarius, for which information on the skeletal systems of the syrinx, hyoid and larynx is lacking - despite these structures having been recognised as performing key functional roles associated with vocalisation, respiration and feeding. Previous research into the syrinx and hyoid have also indicated these structures to be valuable for determining evolutionary relationships among neognath taxa, and thus suggest they would also be informative for palaeognath phylogenetic analyses, which still exhibits strong conflict between morphological and molecular trees., Results: The morphology of the syrinx, hyoid and larynx of C. casuarius is described from CT scans. The syrinx is of the simple tracheo-bronchial syrinx type, lacking specialised elements such as the pessulus; the hyoid is relatively short with longer ceratobranchials compared to epibranchials; and the larynx is comprised of entirely cartilaginous, standard avian anatomical elements including a concave, basin-like cricoid and fused cricoid wings. As in the larynx, both the syrinx and hyoid lack ossification and all three structures were most similar to Dromaius. We documented substantial variation across palaeognaths in the skeletal character states of the syrinx, hyoid, and larynx, using both the literature and novel observations (e.g. of C. casuarius). Notably, new synapomorphies linking Dinornithiformes and Tinamidae are identified, consistent with the molecular evidence for this clade. These shared morphological character traits include the ossification of the cricoid and arytenoid cartilages, and an additional cranial character, the articulation between the maxillary process of the nasal and the maxilla., Conclusion: Syrinx, hyoid and larynx characters of palaeognaths display greater concordance with molecular trees than do other morphological traits. These structures might therefore be less prone to homoplasy related to flightlessness and gigantism, compared to typical morphological traits emphasised in previous phylogenetic studies.

New fossil lungfish remains comprising two parasphenoids, tooth plates and scales from the Famennian Witpoort Formation of South Africa are described. From the parasphenoid material, which bears similarity to Oervigia and Sagenodus but is nevertheless unique, a new genus, Isityumzi mlomomde gen. et sp. nov. is erected. Tooth plates and scales from the same locality may be conspecific but are not yet assigned until further material becomes available. The tooth plates closely resemble those of some taxa in the Carboniferous genus Ctenodus . The new taxon is significant as only the second Devonian lungfish described from the African continent, and for hailing from the high-latitude (polar) Waterloo Farm environment situated close to 70° south during the Famennian., Competing Interests: The authors declare that they have no competing interests., (© 2019 Gess and Clement.)

Neurodegenerative diseases are characterized by the accumulation of misfolded proteins in the brain. Insights into protein quality control mechanisms to prevent neuronal dysfunction and cell death are crucial in developing causal therapies. Here, we report that various disease-associated protein aggregates are modified by the linear ubiquitin chain assembly complex (LUBAC). HOIP, the catalytic component of LUBAC, is recruited to misfolded Huntingtin in a p97/VCP-dependent manner, resulting in the assembly of linear polyubiquitin. As a consequence, the interactive surface of misfolded Huntingtin species is shielded from unwanted interactions, for example with the low complexity sequence domain-containing transcription factor Sp1, and proteasomal degradation of misfolded Huntingtin is facilitated. Notably, all three core LUBAC components are transcriptionally regulated by Sp1, linking defective LUBAC expression to Huntington's disease. In support of a protective activity of linear ubiquitination, silencing of OTULIN, a deubiquitinase with unique specificity for linear polyubiquitin, decreases proteotoxicity, whereas silencing of HOIP has the opposite effect. These findings identify linear ubiquitination as a protein quality control mechanism and hence a novel target for disease-modifying strategies in proteinopathies., (© 2019 The Authors.)

The skull of ' Ligulalepis ' from the Early Devonian of Australia (AM-F101607) has significantly expanded our knowledge of early osteichthyan anatomy, but its phylogenetic position has remained uncertain. We herein describe a second skull of ' Ligulalepis ' and present micro-CT data on both specimens to reveal novel anatomical features, including cranial endocasts. Several features previously considered to link ' Ligulalepis' with actinopterygians are now considered generalized osteichthyan characters or of uncertain polarity. The presence of a lateral cranial canal is shown to be variable in its development between specimens. Other notable new features include the presence of a pineal foramen, the some detail of skull roof sutures, the shape of the nasal capsules, a placoderm-like hypophysial vein, and a chondrichthyan-like labyrinth system. New phylogenetic analyses place ' Ligulalepis ' as a stem osteichthyan, specifically as the sister taxon to 'psarolepids' plus crown osteichthyans. The precise position of 'psarolepids' differs between parsimony and Bayesian analyses., Competing Interests: AC No competing interests declared, (© 2018, Clement et al.)

Lungfishes are the extant sister group of tetrapods. As such, they are important for the study of evolutionary processes involved in the water to land transition of vertebrates. The evolution of a true neck, that is, the complete separation of the pectoral girdle from the cranium, is one of the most intriguing morphological transitions known among vertebrates. Other salient changes involve new adaptations for terrestrial feeding, which involves both the cranium and its associated musculature. Historically, the cranium has been extensively investigated, but the development of the cranial muscles much less so. Here, we present a detailed study of cephalic muscle development in the Australian lungfish, Neoceratodus forsteri, which is considered to be the sister taxon to all other extant lungfishes. Neoceratodus shows several developmental patterns previously described in other taxa; the tendency of muscles to develop from anterior to posterior, from their region of origin toward insertion, and from lateral to ventral/medial (outside-in), at least in the branchial arches. The m.protractor pectoralis appears to develop as an extension of the most posterior m.levatores arcuum branchialium, supporting the hypothesis that the m.cucullaris and its derivatives (protractor pectoralis, levatores arcuum branchialium) are branchial muscles. We present a new hypothesis regarding the homology of the ventral branchial arch muscles (subarcualis recti and obliqui, transversi ventrales) in lungfishes and amphibians. Moreover, the morphology and development of the cephalic muscles confirms that extant lungfishes are neotenic and have been strongly influenced via paedomorphosis during their evolutionary history., (© 2017 Wiley Periodicals, Inc.)

Peripheral or central nerve injury is a frequent cause of chronic pain and the mechanisms are not fully understood. Using newly generated transgenic mice we show that progranulin overexpression in sensory neurons attenuates neuropathic pain after sciatic nerve injury and accelerates nerve healing. A yeast-2-hybrid screen revealed putative interactions of progranulin with autophagy-related proteins, ATG12 and ATG4b. This was supported by colocalization and proteomic studies showing regulations of ATG13 and ATG4b and other members of the autophagy network, lysosomal proteins and proteins involved in endocytosis. The association of progranulin with the autophagic pathway was functionally confirmed in primary sensory neurons. Autophagy and survival were impaired in progranulin-deficient neurons and improved in progranulin overexpressing neurons. Nerve injury in vivo caused an accumulation of LC3b-EGFP positive bodies in neurons of the dorsal root ganglia and nerves suggesting an impairment of autophagic flux. Overexpression of progranulin in these neurons was associated with a reduction of the stress marker ATF3, fewer protein aggregates in the injured nerve and enhanced stump healing. At the behavioral level, further inhibition of the autophagic flux by hydroxychloroquine intensified cold and heat nociception after sciatic nerve injury and offset the pain protection provided by progranulin. We infer that progranulin may assist in removal of protein waste and thereby helps to resolve neuropathic pain after nerve injury., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The first virtual cranial endocast of a lungfish from the Early Devonian, Dipnorhynchus sussmilchi , is described. Dipnorhynchus, only the fourth Devonian lungfish for which a near complete cranial endocast is known, is a key taxon for clarifying primitive character states within the group. A ventrally-expanded telencephalic cavity is present in the endocast of Dipnorhynchus demonstrating that this is the primitive state for "true" Dipnoi. Dipnorhynchus also possesses a utricular recess differentiated from the sacculolagenar pouch like that seen in stratigraphically younger lungfish ( Dipterus, Chirodipterus, Rhinodipterus ), but absent from the dipnomorph Youngolepis . We do not find separate pineal and para-pineal canals in contrast to a reconstruction from previous authors. We conduct the first phylogenetic analysis of Dipnoi based purely on endocast characters, which supports a basal placement of Dipnorhynchus within the dipnoan stem group, in agreement with recent analyses. Our analysis demonstrates the value of endocast characters for inferring phylogenetic relationships., Competing Interests: The authors declare there are no competing interests.

Lungfish first appeared in the geological record over 410 million years ago and are the closest living group of fish to the tetrapods. Palaeoneurological investigations into the group show that unlike numerous other fishes-but more similar to those in tetrapods-lungfish appear to have had a close fit between the brain and the cranial cavity that housed it. As such, researchers can use the endocast of fossil taxa (an internal cast of the cranial cavity) both as a source of morphological data but also to aid in developing functional and phylogenetic implications about the group. Using fossil endocast data from a three-dimensional-preserved Late Devonian lungfish from the Gogo Formation, Rhinodipterus, and the brain-neurocranial relationship in the extant Australian lungfish, Neoceratodus, we herein present the first virtually reconstructed brain of a fossil lungfish. Computed tomographic data and a newly developed 'brain-warping' method are used in conjunction with our own distance map software tool to both analyse and present the data. The brain reconstruction is adequate, but we envisage that its accuracy and wider application in other taxonomic groups will grow with increasing availability of tomographic datasets.