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ABSTRACTIdentification of the diverse animal hosts responsible for spill-over events from animals to humans is crucial for comprehending the transmission patterns of emerging infectious diseases, which pose significant public health risks. To better characterize potential animal hosts of Lassa virus (LASV), we assessed domestic and non-domestic animals from 2021–2022 in four locations in southern Nigeria with reported cases of Lassa fever (LF). Birds, lizards, and domestic mammals (dogs, pigs, cattle and goats) were screened using RT-qPCR, and whole genome sequencing was performed for lineage identification on selected LASV positive samples. Animals were also screened for exposure to LASV by enzyme-linked immunosorbent assay (ELISA). Among these animals, lizards had the highest positivity rate by PCR. Genomic sequencing of samples in most infected animals showed sub-lineage 2 g of LASV. Seropositivity was highest among cattle and lowest in pigs. Though the specific impact these additional hosts may have in the broader virus-host context are still unknown – specifically relating to pathogen diversity, evolution, and transmission – the detection of LASV in non-rodent hosts living in proximity to confirmed human LF cases suggests their involvement during transmission as potential reservoirs. Additional epidemiological data comparing viral genomes from humans and animals, as well as those circulating within the environment will be critical in understanding LASV transmission dynamics and will ultimately guide the development of countermeasures for this zoonotic health threat.

Objective: This study aimed to investigate the impact of diabetes mellitus (DM) on tuberculosis (TB) treatment response using bacterial clearance as a surrogate marker. Method: We compared smear microscopy, culture, and tuberculosis molecular bacterial load assay (TB-MBLA) for treatment monitoring. Following that, bacterial clearance was longitudinally monitored among TB-only (TB without DM) and TB-diabetes (TBDM) patients using TB-MBLA. Results: Ninety-three participants, including 59 TB-only and 34 TBDM patients, were enrolled. TB-only patients exhibited higher upper zone infiltrations (32/35 vs 16/22, p = 0.059) suggesting a trend towards significance, and significantly more cavitation in the same zone (16/18 vs 7/13, p = 0.028). There was a high proportion of Mycobacterium africanum (Maf) among the TBDM cohort (p = 0.0044).At baseline, TB-only patients exhibited a higher average bacterial burden (4.49 logeCFU/mL) compared to the TBDM group (3.91 logeCFU/mL) (p = 0.042). The bacterial load in the TB-only group decreased significantly during treatment but the TBDM group experienced delayed clearance throughout the intensive phase of anti-TB treatment even at day 56 (p = 0.028). The TB-only group demonstrated a shorter median time to TB-MBLA conversion to negative (57 days) compared to the TBDM group (62 days) (p = 0.022). Conclusion: These findings underscore the urgent call for understanding the interplay between diabetes and TB, emphasizing the need for tailored interventions in optimizing TB care for individuals comorbid with diabetes.

Kelainan refraksi atau ametropia adalah penyebab umum gangguan penglihatan yang dibagi menjadi miopi, hipermetropi, astigmatisma, dan presbiopia. Kelainan refraksi tidak dapat dicegah, namun dapat didiagnosis dari pemeriksaan mata dan dapat dikoreksi dengan menggunakan lensa kacamata, lensa kontak dan juga dengan tindakan operasi. Sampai saat ini standar baku emas untuk menghitung status refraksi seseorang masih menggunakan retinoskopi dan refraksi subjektif. Studi pustaka ini bertujuan untuk membahas mengenai perbandingan keakuratan antara hasil retinoskopi dan autorefraktometer untuk menentukan status refraksi seseorang. Metode yang digunakan adalah literature review dengan mencari artikel dengan kata kunci retinoscopy, autorefractometer, dan refractive errors dengan kriteria inklusi meliputi artikel dalam 10 tahun terakhir, akses teks lengkap, baik dalam bahasa Inggris maupun bahasa Indonesia. Kami menemukan 5 penelitian yang membandingkan keakuratan retinoskopi dan autorefraktometer dalam menentukan status refraksi. Autorefraktometer dapat menentukan status refraksi dengan cepat, namun hasilnya dapat overestimated, sedangkan retinoskopi dengan siklopegik memberikan hasil yang lebih akurat namun memerlukan keterampilan dan pengalaman pemeriksa. Studi pustaka ini menyimpulkan bahwa pemeriksaan dengan menggunakan retinoskopi memberikan hasil yang lebih baik dibandingkan dengan autorefraktometer dalam menentukan status refraksi seseorang.

IntroductionGlobally, 11 million children have died before reaching their fifth birthday. The introduction of the Integrated Management of Newborn and Childhood Illness (IMNCI) protocol reduces the morbidity and mortality rates among children under the age of 5. However, the share of neonatal mortality is increasing. As a result, the United Nations has established sustainable development goals to reduce national neonatal death rates through the utilization of the Integrated Management of Newborn and Childhood Illness protocol as the main tool for 12 per 1,000 live births by 2030. However, the death rate from preventable causes has increased owing to the low utilization of the protocol.ObjectiveThe objective of this research is to assess the utilization of the IMNCI protocol and associated factors among healthcare workers (HCW) in health centers at the South Gondar Zone, Northwest Ethiopia, in 2022.MethodsThe institution-based mixed study design was conducted from November to December 2022 at the South Gondar Zone, Amhara. A total of 422 HCW were selected using a computer-generated random-number generator. Data were cleaned and entered into EpiData 3.1 software and analyzed using SPSS version 25.0. Binary logistic regression was used to identify candidates for multivariable logistic analysis with p-value

Submissions of game harvested by hunters per expedition to bushmeat landing depots in Southwestern Nigeria were studied for one year. Three established bushmeat landing depots were purposively selected for the study. Olomore and Kila in Ogun State and Odo Ona in Oyo State. The three were so selected because of their distribution along almost the same line of geographical placement on a line with Kila falling in between the other two on a line. Hunters’ return of harvested game after overnight hunting to the three locations on weekly basis was identified and counted for a year. Twenty-one (21) species of Vertebrates in the class Mammalia, reptiles and birds were returned to the three bushmeat depots by hunters during the study. Location-wise, Olomore had the highest return (1,457) and the least was returned to Kila (987) both in Ogun State. Species-wise, Thryonomys swinderianus (Grasscutter) had the highest population of 2,383 animals with a mean value of 794.3 ± 180.58, followed by Cephalophus maxwelli (duiker) with a mean value of 184.0 ± 32.51. The least hunters’ returns were Bitis gabonica (Black cobra) and Perodicticus potto (Bosmans potto) with a mean value of 0.33 ± 0.58 and 0.67 ± 1.15 respectively.

Stream flow weirs disrupt river flow regimes, physical conditions, and biological composition of rivers, posing significant threat to the river’s functionality, integrity, and sustainability. Home to diverse aquatic organisms, there is a lack of impact assessment of weirs on the stream of the Luvuvhu River Catchment (LRC). The aim of this study was to examine the impact of six weirs on aquatic macroinvertebrate assemblages and composition across five streams. A total of six sampling surveys on macroinvertebrates and physico-chemical parameters were conducted upstream and downstream of six weirs in 12 months between June 2021 and June 2022. The South African Scoring System score (SASS score) and Average Score per Taxon (ASPT) indices were used to compare organisms’ response between upstream and downstream of weirs. Generalized linear mixed models (GLMM) were used to determine the effect of physico-chemical variables on macroinvertebrate assemblage, while the CCA was employed to assess similarities between downstream and upstream sampling points across various sites. A total of 18,914 macroinvertebrate individuals were observed from 65 families during the survey. In upstream sections, the SASS score was driven by habitat integrity, electrical conductivity, and water depth, while ASPT responded significantly to habitat integrity, pH, dissolved oxygen and electrical conductivity. In the downstream sections, the SASS score increased with an increasing habitat integrity score and river width, while decreasing with elevation and pH levels. ASPT increased with increasing habitat integrity and elevation in the downstream sections, while decreasing with increasing river width and water temperature. This study’s findings suggest habitat integrity is largely driving aquatic abundance and assemblage in the LRC, and it is therefore important to maintain the ecological integrity of rivers.

Urolithiasis (UL) is a severe public health concern in southeastern Mexico. Computed tomography (CT) is the first-line diagnostic method for patients with suspected UL. The present study aimed to characterize stones in the entire urinary system using CT and to contribute to personalized treatment in patients with UL. Patients >18 years of age with suspected UL were enrolled. Characteristics of UL included stone size, location (kidney, ureters, and bladder), composition of the stone in Hounsfield units (HU), presence of staghorn stone(s), and obstructive uropathy. Patients were stratified according to sex and age to determine whether stone size and HU were dependent on hormonal factors in females and on prostatic hyperplasia in males. The Mann–Whitney U test was used to compare median values. Frequencies are expressed as percentages and were analyzed using the Mantel–Haenszel chi-squared test. A total of 1150 patients were included in this study, of whom 744 (64.7 %) had UL in only 1 anatomical location in the urinary system, and 406 (35.3 %) had stones in ≥2 anatomical locations. Localization and stone size differed between males and females (p 50 years). In addition, females exhibited statistical differences in HU (p = 0.010) and kidney stone size (p = 0.047) dependent on age (≤47 and > 47 years). In conclusion, findings suggest that HU and stone size differ in different anatomical structures of the urinary system. In addition, differences in stone size and composition may be associated with age and sex.

Radon is a radioactive gas and a leading cause of lung cancer among non-smokers. An indicator of the level of risk associated with radon inhalation is the Geogenic Radon Potential (GRP) - a function of the soil gas radon concentration and the soil air permeability. Data is scarce on the variation of soil gas radon and GRP across different geological formations in southwest Nigeria. This study was designed to measure and develop a generalized predictive model for soil gas radon concentration and hence GRP on different bedrocks in southwest Nigeria. Soil gas radon was measured with a RAD 7 radon detector in 150 sites randomly selected over 20 major bedrocks. Soil air permeability was derived from soil saturated hydraulic conductivity measured using a constant head permeameter on undisturbed soil samples from the same sites. The GRP was obtained using Neznal relation. A 2 × 8 x 1 Artificial Neural Network (ANN) configuration culminated in the generation of a tested and validated predictive model for soil gas radon in southwest Nigeria. For the 150 sites, the range of values for soil gas radon concentration was 0.28–47.59 kBqm−3 and a mean of 10.39 ± 12.59 kBqm−3; soils on granitic bedrocks had the highest mean soil gas radon concentration (16.89 kBqm−3) and highest mean GRP (13.71). Sediments had the highest mean soil air permeability of 39.84 × 10−12 m2. Using Neznal classification, 75.30% of the sites were of low radon hazard rating. The developed predictive ANN model had a Goodness-of-Prediction (G) of 73.53%, Average Validation Error (AVE) of 0.073, Mean Bias Error (MBE) of 0.42, and Root Mean Square Error (RMSE) of 4.62kBqm−3, respectively. The model, validated using standard procedure had G, MBE, AVE, and RMSE of 86.49%, 0.61, 0.17, and 1.65kBqm−3, respectively which is an indication of good model performance.

BackgroundThe epidemiology of Mycobacterium tuberculosis complex (MTBC) lineage 5 (L5) infections in Ghana revealed a significantly increased prevalence in Ewes compared to other self-reported ethnic groups. In that context, we sought to investigate the early phase of tuberculosis (TB) infection using ex vivo infection of macrophages derived from the blood of Ewe and Akan ethnic group volunteers with MTBC L4 and L5 strains.MethodsThe study participants consisted of 16 controls, among which self-reported Akan and Ewe ethnicity was equally represented, as well as 20 cured TB cases consisting of 11 Akans and 9 Ewes. Peripheral blood mononuclear cells were isolated from both healthy controls and cured TB cases. CD14+ monocytes were isolated and differentiated into monocyte-derived macrophages (MDMs) before infection with L4 or L5 endemic strains. The bacterial load was assessed after 2 hours (uptake) as well as 3 and 7 days post-infection.ResultsWe observed a higher capacity of MDMs from Ewes to phagocytose L4 strains (p < 0.001), translating into a higher bacillary load on day 7 (p < 0.001) compared to L5, despite the higher replication rate of L5 in Ewe MDMs (fold change: 1.4 vs. 1.2, p = 0.03) among the controls. On the contrary, within macrophages from Akans, we observed a significantly higher phagocytic uptake of L5 (p < 0.001) compared to L4, also translating into a higher load on day 7 (p = 0.04). However, the replication rate of L4 in Akan MDMs was higher than that of L5 (fold change: L4 = 1.2, L4 = 1.1, p = 0.04). Although there was no significant difference in the uptake of L4 and L5 among cured TB cases, there was a higher bacterial load of both L4 (p = 0.02) and L5 (p = 0.02) on day 7 in Ewe MDMs.ConclusionOur results suggest that host ethnicity (driven by host genetic diversity), MTBC genetic diversity, and individual TB infection history are all acting together to modulate the outcome of macrophage infections by MTBC.

The efficiency of physical separation techniques of heavy minerals usually encounters some set-backs. The reason is often not far from the inability to develop suitable mineral characterization strategies in order to comprehend/evaluate certain physicochemical features such as surface chemistry, specific gravity difference, magnetic and electrical responses distributed among the mineral particles. The intense need for the development/advancement of efficient gravity concentration route on heavy minerals, more especially for the recovery and upgrade of fine, near-dense, low-grade heavy mineral deposits cannot be over-emphasized. However, the process application of gravity concentration on heavy minerals has not been widely investigated, and has often times been neglected. Existing literature on investigations conducted does not completely incorporate process routes, operating principles, parameters and applications; and as such, information in this area is somewhat scanty, hence the purpose of this study. A bulk of more recently developed gravity concentration medium such as enhanced gravity concentrations possess essential potentials which can be applied in certain physical beneficiation routes. On this premise, the need for further investigation is highly imperative. This review is therefore aimed at revealing the advantageous features of enhanced gravity concentrations over the conventional techniques, as well as the process selection for optimal beneficiation and high-grade yields. Thus, process applications, operating mechanism/principles, general performance evaluation in treating/upgrading heavy minerals using gravity techniques, the merits/shortcomings involved in conventional/enhanced gravity concentrators and recommendations have been captured in this review. This study will thus contribute greatly to the body of knowledge in the physical treatment/concentration of heavy minerals.

AbstractMany freshwater ecosystems are facing ecological challenges such as influx of trace elements from human activities, and sediments behave as a sink for trace elements in these environments. Trace element contamination in river sediments is a major environmental concern due to its devastating effect on benthic organisms. The aim of this study was to assess the effect of trace elements in sediments on the distribution of benthic macroinvertebrates in the Blyde and Mohlapitsi rivers of the Olifants River Basin, South Africa. Sediment samples and benthic macroinvertebrates were collected from six sites along each river. The results showed variations in the concentration of the trace elements in the sediment and the distribution of benthic macroinvertebrates among the different sites and between the two rivers. Both rivers recorded high taxa richness and sensitive taxa were well represented in most parts of the rivers, an indication that the rivers are not highly disturbed. There were insignificant correlations between most of the trace elements and the abundance of the benthic macroinvertebrates, though some taxa showed significant correlations with the trace elements. Despite the low impact of the trace elements on the distribution and diversity of benthic macroinvertebrates, ecological health of the rivers and structural distribution of macroinvertebrates may be affected in the future due to increasing human activities in the catchments. It is therefore recommended that effluents from human activities should be controlled to prevent a further degradation of the rivers to protect macroinvertebrates and other aquatic biota.

From time immemorial there have been diverse opinions and presuppositions about the subject of faith and the subject of reason in both theology and philosophy from different schools of thought in the west and even in African Christianity. Some theologians have considered faith and reason as being incompatible and as two parallel lines that can never meet; the early Christian writer Tertullian asked, “What has Athens to do with Jerusalem? What is the relationship between the church and the Academy? These rhetorical questions suggest that the conflict between faith and reason is real and not just imaginary. Other schools of thought see no discord between faith and reason and thereby conclude that the seeming rift between the duo is just founded on human imagination. Nevertheless, faith and reason are seen as the two ‘wings’ upon which theology or religion thrive and sustain themselves in comprehending religious concepts and beliefs. Consequently, there abound diverse hypothesis and presupposition about the duo (faith and reason). Various schools of thought exist in history and in the contemporary scene on the controversy, rift and conflict between faith and reason, fideism and rationalism. Rhetorically, is the conflict between faith and reason real or imaginary? Consequently, this paper addresses the historical overview of the concept of faith and reason, the conflict between faith and reason and the equilibrium cum negotiation therein. The research method employed was a historical-analytical one.

Benthic macroinvertebrates play a vital role in ecosystem functioning, such as nutrient cycling, primary production, decomposition and material translocation. A study was done to determine the functional feeding groups (FFGs) distribution along two streams of the Olifants River System, South Africa. There were longitudinal differences of the functional groups but were more pronounced in the Dwars River than in the Spekboom River. Collector-gatherers and collector-filterers were the most abundant groups recorded in both rivers. The least abundant groups were the shredders and scrapers in both rivers. The highest abundance of shredders in both rivers was at upstream sites (DS1 and SS1), more scrapers were found at midstream sites (DS3 and SS2), collector-gatherers and collector-filterers increased in the downstream (SS4) of the Spekboom River and predators were nearly constant in relative abundance at all sites. The relative abundance and richness of the FFGs did not conform completely to the river continuum concept (RCC). This could be related to the degradation of the catchment resulting from human activities which affected the quality of the water.

The important of the role of women in the life of the church cannot be over-emphasized. This is because research shows that larger percentages of church attendants who are active members are women. Incidentally, directly or indirectly most women are relegated to the background in terms of leadership position in the church probably due to cultural bias or the patriarchal nature and tradition of various culture and the Holy writ. This paper adopts an analytical and theological method in presenting the ecclesiological analysis of women leadership and the reflection thereof. Research shows that the majority of women throughout the world are still suffering from systemic trends of violence, inequality, discrimination, abuse, and neglect at home, in the labour market, church, and in society at large. Also, a second century Rabbi named Judah, Ben Ilai exclaimed: “Thank God I am not a woman, a slave, or a pagan” and down the centuries, many have also exclaimed the same sigh of relief. Some, even within Evangelicalism today, consented that this is the reason why Jesus chose twelve men to be the future leaders of the church and probably why Paul told Timothy not to permit a woman to teach in the church or have authority over a man; this in a sense is a sweeping generalization. Nevertheless, women as followers in the church play a significant roles in the composition of and roles within the church. Therefore, women in one way or another participate in the leading of the church as they influence the leadership of the church in diverse ways. Consequently, this paper examines the concept of Ecclesiology and women leadership and the theological reflection thereof.

The New Testament was written to the audience of the Graeco-Roman world of which the authorial intentions were crystal clear to the then audiences. There is the temptation of eisegesis in the application of the text to the Nigerian context which of course differs in many ways to those of early societies. Consequently, there is the need for the New Testament to be ‘more at home’ within the Nigerian cultural milieu and worldview for it to be relevant to the Nigerian culture. The New Testament was written within a specific context and it needs to be decontextualized from the Graeco-Roman culture and re-contextualized to suit the Nigerian Context and culture for proper contextualization and enculturation to occur. Inculturation is a term that is also applied to denote a progression of engagement between the Christian Gospel and specific cultures. The term is proposed conceptually both to defend the integrity of the Gospel and to encourage understanding to numerous cultural contexts. The method adopted in this study is a theologico - analytico method which emanates from the application of the methods and concepts of late-twentieth-century analytic philosophy (Wood, 2021). African inculturation theology is in essence a contextual theology that pursues an agenda to make the Holy Gospel far more meaningful within diverse cultural milieus. In this article the milieu is Nigeria. This type of theology has an important religious aim, which is essentially to make the Gospel all culturally embracing to non-Europeans. Without a contextual theology serving any missionizing activity it is difficult to make the gospel message totally understandable in any particular context. It makes it harder to motivate people to deeper faith and to equip ministers more faithfully and effectively to preach the gospel.

Abstract The impact of anthropogenic activities such as mining, agriculture and urbanization is causing heavy metal contamination in many freshwater ecosystems. The concentrations of eight elements (As, Cr, Cu, Fe, Mn, Ni, Pb and Zn) in the Spekboom River, South Africa, were studied using enrichment factor (EF) and geo-accumulation index (Igeo) to assess the extent of pollution in the river. Sediment samples were collected and analyzed using sequential inductively coupled plasma—optical emission spectrometry. The results showed deterioration of the sediment quality with high concentration of Cr and Ni at all the sites, this is a reflection of contamination from the various anthropogenic activities in the area. The current levels of Cr and Ni could be detrimental to the river and may pose a serious threat to the aquatic organisms and humans, as the sediment could act as a secondary source of metal pollution in the water. It is therefore recommended that urgent action should be taken to control effluents from anthropogenic activities to the river in order to prevent further pollution.

Abstract Aim This study examines interrelations between gains of Norton Scale Score (NSS) and functional outcome measured by Functional Independence Measurement (FIM) among older hip fracture patients. Design Retrospective study. Methods We examined 227 patients consecutively hospitalized in a geriatric postacute rehabilitation ward. The data were collected during 2012‐2017. Data were analysed using Student's t test, chi‐square test, Pearson's correlation coefficient and linear regression. Results Patients with positive NSS gains demonstrated statistically significant higher total FIM, motor FIM and total FIM gain scores at hospital discharge, compared with patients showing no NSS gains or negative NSS. Multiple regression analysis indicated that positive NSS gains were independently predictive for higher total FIM and motor FIM scores at hospital discharge and higher motor FIM gains at discharge. Conclusion Our results suggest that positive NSS gains are associated with higher FIM scores at hospital discharge and may assist in predicting the functional outcome of hospitalized older hip fracture patients.

The recent interest in the applications of mineral rocks for interior building decoration has been a major concern from the radiological perspective because the breaking down of rocks into various shapes and sizes releases radioactive gaseous element that is harmful to human health. Hence, this study assessed the radon exhalation rates of different rock types in Nigeria and their implications on human health. A total of 45 samples comprising five samples per rock type were prepared, packed, and sealed inside a modified closed can and thereafter subjected to radon concentration measurement using a RAD7 detector. The results of the study showed that granite and limestone rock types had high radon concentrations and exhalation rates as compared to other rock samples assessed. The radon concentration for granite and limestone rockfalls within the action level limit. Thus, effort should be made to ensure adequate ventilation of any building that uses these rock types in building decoration. The results obtained can be used as baseline data for future investigation of the rock types in any locality.

Globally, many freshwater ecosystems are facing chemical pollution from both natural and anthropogenic sources. The Olifants River Basin in South Africa is experiencing degradation due to mining, industrial, agricultural, and domestic activities. The impacts of these activities coupled with climate change is likely to shift the hydrological cycle that may increase accumulation of toxic chemicals in the sediments. The aim of the study was to assess the contamination of As, Cr, Cu, Fe, Mn, Ni, Pb, and Zn in the sediments collected at the upstream, midstream and downstream of four rivers of the Lower Olifants River Basin; the Blyde, Mohalpitsi, Ga-Selati, and Steelpoort rivers. The highest concentrations of most of the trace metal (loid)s assessed were from the Steelpoort River followed by the Blyde River. Significant differences in metal concentrations were found across study sites and rivers. The overall assessment of the sub-catchment, which is characterised mainly by mining and agricultural activities shows significantly elevated levels of As, Cr, Mn, and Ni in the sediments and may cause secondary pollution in the water. Using enrichment factor (EF) and geo-accumulation index (Igeo), some of the sediments were severely enriched and extremely contaminated respectively with As, Cr, and Ni. This may risk the lives of aquatic biota and humans, especially rural communities that rely on these rivers for drinking water. The findings provide baseline information for effective management control of metal(loid) pollution in the Olifants River Basin.

The development of photocatalysts with wide spectral absorption and high charge separation efficiency has always been a pursued objective for photocatalytic solar energy conversion. Herein, we reported a wide-range visible-light-active Bi4TaO8Cl (BTOC) single crystal nanoplate with dominating {110} and {001} facets for enhancing the intrinsic charge separation efficiency. Insitu selective photodeposition of metals and metal oxides provides evidences of photogenerated electrons and holes spatially separated on {110} and {001} coexposed facets of BTOC, respectively. The intrinsic charge separation efficiency was demonstrated to be closely dependent on the crystal facets, which can be modulated by tuning the coexposed crystal facet ratio. Further surface modification of BTOC with suitable dual cocatalyst Ag and RuOx enables remarkable improvement of charge separation efficiency and photocatalytic water oxidation performance. Investigation by comparison between well-defined BTOC nanoplate and BTOC nanoparticles confirmed the significance of coexposed crystal facets for efficient spatial charge separation and the blocking of reverse reaction from Fe2+ to Fe3+ ions during water oxidation reaction, indicating that rational modulation of exposed crystal facets is significant for controlling the intrinsic charge separation efficiency on Bi4TaO8Cl photocatalyst for efficient photocatalytic water splitting.

This research was aimed at evaluating the efficiency of advanced gravity and magnetic separations on the recovery of chromite from the fine Platinum Group Metals (PGM) tailings consisting of particles 80% passing 75 µm with about 45% being >45 µm resulting in high chromite losses. The PGM plant tailings were subjected to X-ray fluorescence, scanning electron microscopy and particle size distribution analyses. The feed was then optimally classified with 60 mm diameter hydro-cyclone into underflow and overflow streams. The coarser underflow was further beneficiated using the spiral concentrator. The results obtained showed that the removal of fines increased the Cr2O3 grade for the spiral feed from 12.27% to 17.64% while spiral concentrate grade improved from 14.84% to 21.46% and recovery 69.85% to 95.53%. Magnetic separation efficiency was found to increase with particle size such that at >75 µm a concentrate with up to 17.13% grade and 61.5% recovery was achieved. The advanced Falcon concentration was also observed to be mainly particle size dependent and at 45 µm up to 17% grade and 60.3% recovery was achieved. The results obtained are based on particles >45 µm and the finer particles

Biomagnification of Hg and persistent organic pollutants (POPs: polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), polybrominated diphenyl ethers (PBDEs)) in aquatic food chains can lead to high pollutant concentrations in top predators, including humans. Despite this threat to human health, research concerning bioaccumulation is still underrepresented in the southern hemisphere and in (sub)arctic and (sub)tropical areas, emphasizing the need for research in these locations. In this study, samples of water, sediment and aquatic biota were analyzed to determine concentrations of POPs and total mercury (THg) in the Ga-Selati river (South Africa) and two rivers Rena and Gudbrandsdalslågen in Norway. Trophic magnification factors (TMFs) were determined to evaluate and compare the biomagnification and the threat to human health due to consumption of the fish was assessed.Concentrations of POPs in sediment and biota samples were generally low except for relatively high concentrations of ∑DDX (dichlorodiphenyltrichloroethane and metabolites) in aquatic biota from the Ga-Selati river (ranging from 1.9 to 133 ng/g ww in invertebrates and 1.9 to 5643 ng/g ww in fish). Dissolved THg concentrations were high in the Ga-Selati river (ranging from 0.009 to 0.036 μg/l) but THg concentrations in sediment and biota were low in studied rivers compared to other studies. Biomagnification occurred for THg, several DDT-metabolites and PCB compounds, TN and CN. Biomagnification of p,p′-DDT and THg differed significantly between the two countries, supporting existing patterns found in literature, although more data is needed to attribute these differences to climatic or other factors. Concentrations in fish from the rivers Ga-Selati and Rena were under the threshold levels reported for THg and POPs, but caution should be taken when consuming Northern pike (Esox Lucius) from the subarctic river Gudbrandsdalslågen, to avoid harmful effects due to both elevated THg and PBDE exposure. Keywords: Persistent organic pollutants, Hg, Bioaccumulation, Trophic magnification factors, South Africa, Norway

Animal feed has been linked to human illness through the food chain as a result of food borne bacteria and more recently the risk of foodborne antibiotic resistance. This study investigated the extent to which radiation can be used as an intervention to improve the safety and quality of poultry feed in terms of food borne pathogens and antibiotic resistant microbes. Mean counts of control feed samples were Log10 5.98 for total viable count (TVC), Log10 4.76 for coliform count (CC), Log10 2.89 for Staphylococcus aureus count (STC), and Log10 4.57 for yeast and mold count (YMC) and Salmonella spp. (SC) was not detected (ND). All counts were within permissible levels except for CC (Log10 4.76) which was above the permissible limit of ≤ log10 4.0. Identified bacteria isolates were Enterobacter cloacae (54.5%), Bacillus cereus (27.3%), and Klebsiella pneumoniae (18.2%). All (100%) isolates exhibited multidrug Resistance (MDR) with Bacillus cereus being the most resistant (to 9 out of 11 antibiotics) followed by Enterobacter cloacae/Klebsiella pneumoniae (4 out of 11 antibiotics). Several resistance patterns were observed with PEN/AMP/FLX being the commonest (100%), followed by ERY (90.9%), TET (72.7%), CRX (66.6%), CTX (45.4%), CHL/CTR (36.4%), GEN (27.3%), and COT (18.2%). Klebsiella pneumoniae showed zero resistance to GEN/CHL/CTR/CTX/CRX while Enterobacter cloacae and Bacillus cereus exhibited zero resistance to GEN and COT, respectively. The most effective antibiotic against Gram negative bacteria (Enterobacter cloacae and Klebsiella pneumoniae) was gentamicin while cotrimoxazole was the most effective against Bacillus cereus (Gram positive). Radiation processing of 5kGy totally eliminated all microbes including MDR food borne pathogens. In view of this, we recommend low dose radiation decontamination as a measure to mitigate against the possible food safety and public health risks to humans associated with poultry feed.

Tujuan penelitian ini untuk mengetahui pengaruh penambahan fly ash dan ser­­buk batu gamping terhadap perubahan temperatur. Penelitian dilakukan dengan uji kuat tekan pada 40 silinder be­ton ukuran 15 cm x 30 cm. Kelompok kontrol adalah 20 be­ton normal, kelompok eksperimen adalah 20 ben­da uji yang diberi 25,00% fly ash dan 15,00% serbuk batu gamping dari berat total se­men. Hasil penelitian me­nun­juk­kan bahwa dalam keadaan tidak dibakar terdapat per­bedaan kuat tekan beton antara be­ton normal sebesar 256,65 kg/cm2 dan beton dengan pe­nambahan fly ash dan ser­buk batu gamping sebesar 325,85 kg/cm2. Tidak terdapat pebedaan perubahan nilai kuat tekan beton akibat pembakaran antara beton normal dan beton dengan tambahan fly ash dan serbuk batu gamping. Akibat pembakaran pada suhu 400°C selama satu jam, beton normal dan beton dengan tambahan fly ash dan serubuk batu gamping meng­alami pe­nurunan nilai kuat tekan sebesar 5,17% dan 5,16%.

Currently existing business competition is not only limited to the quality of products, technology products, and display products, but also about the brand used in the product that can cause an image to consumers. Brand is the label that carries meaning and associations as well as a mirror of promise communicated by the producer to the consumer on the quality of products or services that have been produced. This study aims to determine whether the brand awareness, brand association, perceived quality, brand loyalty and other proprietary brand assets Samsung has a positive contribution to brand equity Samsung, knowing which variable dominant contributes positively to brand equity Samsung, and find out whether brand equity Samsung influence the purchasing decisions of Samsung smartphone products. By using principal component analysis and simple linear regression analysis, the result is Samsung’s brand awareness, brand association, perceived quality, brand loyalty, and other proprietary brand assets are able to contribute positively to the Samsung brand equity. Samsung's brand loyalty is the dominant variable that contributes positively to the Samsung brand equity. Samsung's brand equity have positive significant influence on purchasing decisions Samsung smartphone products.

Introduction: Momordica charantia has been investigated for its effect on various organs and its numerous indications have been cited in literature. There are, however, scanty publications on its effect on the male reproductive system. Objective: To evaluate the effects of methanolic seed extract of M. charantia (MC) on the sperm production (sperm number and motility), testicular volume and testicular testosterone in Sprague–Dawley (S–D) rats. Materials and methods: Twenty adult male S–D rats, weighing 106–200 g allotted randomly into four main groups (A, B, C and D). Groups A, B and C received 15, 25 and 50 mg/100 g b.w/oral of MC, respectively, daily. Group IV rats (control) were fed equal volume of physiological saline. The duration of treatment for both extract and physiological saline was 56 days. The animals were sacrificed by cervical dislocation. Testicular volume, sperm count and motility and testicular testosterone estimated. Results: The sperm number and motility were found to be significantly decreased (p

Background: The co-use of nicotine and cannabis has been steadily rising in the United States. Rodent studies suggest that delta-9-tetrahydrocannabinol (THC) could increase addictive qualities of nicotine, but whether repeated THC exposure alters self-administration of nicotine has not been tested. We hypothesized that THC would increase the reinforcing effects of nicotine and alter nicotine intake., Methods: Adult male and female Sprague-Dawley rats were treated with THC (0, 3, 30 mg/kg) daily for 14 days prior to and during training for intravenous self-administration of nicotine. Rats were allowed to self-administer nicotine for several weeks, then tested for sensitivity to nicotine dose through multiple determinations of a nicotine dose-effect curve with or without THC pretreatment. A separate set of rats were trained on fixed ratio responding for sucrose and assessed for THC effects on behavior., Results: Post-session THC decreased nicotine self-administration in male and female rats throughout acquisition and maintenance and increased the latency to stable rates of nicotine intake during acquisition. Post-session THC shifted nicotine dose-effect curves downward, and pre-session THC suppressed responding at higher nicotine doses. Unlike nicotine, responding for sucrose was not affected by post-session THC. Pre-session THC decreased responding for sucrose, particularly for THC-naïve rats., Conclusions: Repeated post-session THC decreased nicotine-taking behaviors but did not alter sucrose responding. Thus, post-session THC may alter sensitivity to nicotine. Pre-session THC treatment decreased lever pressing in both sucrose and nicotine studies, indicating this effect was nonspecific. These studies show that THC modulates patterns of nicotine intake in rat models., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Chromodomain helicase DNA-binding protein 1 like (CHD1L) is an oncogene implicated in tumor progression, multidrug resistance, and metastasis in many types of cancer. In this article, we described the optimization of the first lead CHD1L inhibitors (CHD1Li) through drug design and medicinal chemistry. More than 30 CHD1Li were synthesized and evaluated using a variety of colorectal cancer (CRC) tumor organoid models and functional assays. The results led to the prioritization of six lead CHD1Li analogues with improved potency, antitumor activity, and drug-like properties including metabolic stability and in vivo pharmacokinetics. Furthermore, lead CHD1Li 6.11 proved to be an orally bioavailable antitumor agent, significantly reducing the tumor volume of CRC xenografts generated from isolated quasi mesenchymal cells (M-phenotype), which possess enhanced tumorigenic properties. In conclusion, we reported the optimization of first-in-class inhibitors of oncogenic CHD1L as a novel therapeutic strategy with potential for the treatment of cancer.

Taro ( Colocasia esculenta ) and tannia ( Xanthosoma sp.) plants growing in 25 districts across Ethiopia, Kenya, Tanzania and Uganda were surveyed for four RNA viruses. Leaf samples from 392 plants were tested for cucumber mosaic virus (CMV), dasheen mosaic virus (DsMV), taro vein chlorosis virus (TaVCV) and Colocasia bobone disease-associated virus (CBDaV) by RT-PCR. No samples tested positive for TaVCV or CBDaV, while CMV was only detected in three tannia samples with mosaic symptoms from Uganda. DsMV was detected in 40 samples, including 36 out of 171 from Ethiopia, one out of 94 from Uganda and three out of 41 from Tanzania, while none of the 86 samples from Kenya tested positive for any of the four viruses. The complete genomes of nine DsMV isolates from East Africa were cloned and sequenced. Phylogenetic analyses based on the amino acid sequence of the DsMV CP-coding region revealed two distinct clades. Isolates from Ethiopia were distributed in both clades, while samples from Uganda and Tanzania belong to different clades. Seven possible recombination events were identified from the analysis carried out on the available 15 full-length DsMV isolates. Nucleotide substitution ratio analysis revealed that all the DsMV genes are under strong negative selection pressure., Competing Interests: The authors declare they have no conflict of interest., (© 2021 The Authors. Annals of Applied Biology published by John Wiley & Sons Ltd on behalf of Association of Applied Biologists.)

Stress-induced release of dynorphins (Dyn) activates kappa opioid receptors (KOR) in serotonergic neurons to produce dysphoria and potentiate drug reward; however, the circuit mechanisms responsible for this effect are not known. In male mice, we found that conditional deletion of KOR from Slc6a4 (SERT)-expressing neurons blocked stress-induced potentiation of cocaine conditioned place preference (CPP). Within the dorsal raphe nucleus (DRN), two overlapping populations of KOR-expressing neurons: Slc17a8 (VGluT3) and SERT, were distinguished functionally and anatomically. Optogenetic inhibition of these SERT + neurons potentiated subsequent cocaine CPP, whereas optical inhibition of the VGluT3 + neurons blocked subsequent cocaine CPP. SERT + /VGluT3 - expressing neurons were concentrated in the lateral aspect of the DRN. SERT projections from the DRN were observed in the medial nucleus accumbens (mNAc), but VGluT3 projections were not. Optical inhibition of SERT + neurons produced place aversion, whereas optical stimulation of SERT + terminals in the mNAc attenuated stress-induced increases in forced swim immobility and subsequent cocaine CPP. KOR neurons projecting to mNAc were confined to the lateral aspect of the DRN, and the principal source of dynorphinergic (Pdyn) afferents in the mNAc was from local neurons. Excision of Pdyn from the mNAc blocked stress-potentiation of cocaine CPP. Prior studies suggested that stress-induced dynorphin release within the mNAc activates KOR to potentiate cocaine preference by a reduction in 5-HT tone. Consistent with this hypothesis, a transient pharmacological blockade of mNAc 5-HT 1B receptors potentiated subsequent cocaine CPP. 5-HT 1B is known to be expressed on 5-HT terminals in NAc, and 5-HT 1B transcript was also detected in Pdyn + , Adora2a + and ChAT + (markers for direct pathway, indirect pathway, and cholinergic interneurons, respectively). Following stress exposure, 5-HT 1B transcript was selectively elevated in Pdyn + cells of the mNAc. These findings suggest that Dyn/KOR regulates serotonin activation of 5HT 1B receptors within the mNAc and dynamically controls stress response, affect, and drug reward., (© 2021. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.)

Behavioral stress exposure increases the risk of drug-taking in individuals with substance use disorders by mechanisms involving the dynorphins, which are the endogenous neuropeptides for the kappa opioid receptor (KOR). KOR agonists have been shown to encode dysphoria, aversion, and changes in reward valuation, and kappa opioid antagonists are in clinical development for treating substance use disorders. In this study, we confirmed that KORs were expressed in dopaminergic neurons in the ventral tegmental area (VTA) of male C57BL6/J mice. Genetic ablation of KORs from dopamine neurons blocked the potentiating effects of repeated forced swim stress on cocaine conditioned place preference (CPP). KOR activation inhibited dopamine neuron GCaMP6m calcium activity in VTA during swim stress and caused a rebound enhancement during the period after stress exposure. Transient optogenetic inhibition of VTA dopamine neurons with AAV5-DIO-SwiChR was acutely aversive in a real time place preference assay and blunted cocaine CPP when inhibition was administered concurrently with cocaine conditioning. However, when inhibition preceded cocaine conditioning by 30 min, cocaine CPP was enhanced. Retrograde tracing with CAV2-DIO-ZsGreen identified a population of prodynorphin Cre neurons in the dorsal raphe nucleus (DRN) projecting to the VTA. Optogenetic stimulation of dynorphinergic neurons within the DRN by Channelrhodopsin2 activated KOR in VTA and ablation of prodynorphin blocked stress potentiation of cocaine CPP. Together, these studies demonstrate the presence of a dynorphin/KOR midbrain circuit that projects from the DRN to VTA and is involved in altering the dynamic response of dopamine neuron activity to enhance drug reward learning., Competing Interests: Declaration of Competing Interest None.

Following repeated opioid use, some dependent individuals experience persistent cognitive deficits that contribute to relapse of drug-taking behaviors, and one component of this response may be mediated by the endogenous dynorphin/kappa opioid system in neocortex. In C57BL/6 male mice, we find that acute morphine withdrawal evokes dynorphin release in the medial prefrontal cortex (PFC) and disrupts cognitive function by activation of local kappa opioid receptors (KORs). Immunohistochemical analyses using a phospho-KOR antibody confirmed that both withdrawal-induced and optically evoked dynorphin release activated KOR in PFC. Using a genetically encoded sensor based on inert KOR (kLight1.2a), we revealed the in vivo dynamics of endogenous dynorphin release in the PFC. Local activation of KOR in PFC produced multi-phasic disruptions of memory processing in an operant-delayed alternation behavioral task, which manifest as reductions in response number and accuracy during early and late phases of an operant session. Local pretreatment in PFC with the selective KOR antagonist norbinaltorphimine (norBNI) blocked the disruptive effect of systemic KOR activation during both early and late phases of the session. The early, but not late phase disruption was blocked by viral excision of PFC KORs, suggesting an anatomically dissociable contribution of pre- and postsynaptic KORs. Naloxone-precipitated withdrawal in morphine-dependent mice or optical stimulation of pdyn Cre neurons using Channelrhodopsin-2 disrupted delayed alternation performance, and the dynorphin-induced effect was blocked by local norBNI. Our findings describe a mechanism for control of cortical function during opioid dependence and suggest that KOR antagonism could promote abstinence., (© 2021. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.)

Epithelial-mesenchymal transition (EMT) is a driving force in promoting malignant cancer, including initiation, growth, and metastasis. EMT is a dynamic process that can undergo a mesenchymal-epithelial transition (MET) and partial transitions between both phenotypes, termed epithelial-mesenchymal plasticity (EMP). In cancer, the acquisition of EMP results in a spectrum of phenotypes, promoting tumor cell heterogeneity and resistance to standard of care therapy. Here we describe a real-time fluorescent dual-reporter for vimentin and E-cadherin, biomarkers of the mesenchymal and epithelial cell phenotypes, respectively. Stable dual-reporter cell lines generated from colorectal (SW620), lung (A549), and breast (MDA-MB-231) cancer demonstrate a spectrum of EMT cell phenotypes. We used the dual-reporter to isolate the quasi epithelial, epithelial/mesenchymal, and mesenchymal phenotypes. Although EMT is a dynamic process, these isolated quasi-EMT-phenotypes remain stable to spontaneous EMP in the absence of stimuli and during prolonged cell culture. However, the quasi-EMT phenotypes can readily be induced to undergo EMT or MET with growth factors or small molecules. Moreover, isolated EMT phenotypes display different tumorigenic properties and are morphologically and metabolically distinct. 3D high-content screening of ~23,000 compounds using dual-reporter mesenchymal SW620 tumor organoids identified small molecule probes that modulate EMT, and a subset of probes that effectively induced MET. The tools, probes, and models described herein provide a coherent mechanistic understanding of mesenchymal cell plasticity. Future applications utilizing this technology and probes are expected to advance our understanding of EMT and studies aimed at therapeutic strategies targeting EMT.

Since its first report in 1956 by Puck and Marcus, the clonogenic assay has not been completely adapted into high-content-screening (HCS) workflows despite the numerous automated systems available. Initially, clonogenic assays were used to observe the effects of radiation on cell survival, particularly with cancer cells. The clonogenic assay has since been well characterized as a measure of cancer stem cell (CSC) stemness, demonstrating that a single CSC can generate clonogenic colonies. CSCs are highly tumorigenic with an unlimited proliferation potential and capacity to generate malignant tumors. Furthermore, CSCs are also known to resist conventional chemotherapy as well as more contemporary targeted therapies alike. Therefore, given the complexity of CSCs and their clinical relevance, new methods must follow to more effectively study and characterize CSC mechanisms that allow them to proliferate and persist, and to develop drugs and other therapies that can more effectively target these populations. Herein, we present a HCS method to quantify the number and size of colonies in 2D and 3D culture models and to distinguish colonies based on fluorescent markers using an Opera Phenix high-content-screening system. In addition, we present a method to scan at low magnification and rescan at a higher magnification to capture in greater detail colonies or even single cells of interest. These methods can be adapted to numerous applications or other imaging systems to study CSC biology using high-content analysis and for high-throughput drug discovery.

Since the discovery of CHD1L in 2008, it has emerged as an oncogene implicated in the pathology and poor prognosis of a variety of cancers, including gastrointestinal cancers. However, a mechanistic understanding of CHD1L as a driver of colorectal cancer has been limited. Until now, there have been no reported inhibitors of CHD1L, also limiting its development as a molecular target. We sought to characterize the clinicopathologic link between CHD1L and colorectal cancer, determine the mechanism(s) by which CHD1L drives malignant colorectal cancer, and discover the first inhibitors with potential for novel treatments for colorectal cancer. The clinicopathologic characteristics associated with CHD1L expression were evaluated using microarray data from 585 patients with colorectal cancer. Further analysis of microarray data indicated that CHD1L may function through the Wnt/TCF pathway. Thus, we conducted knockdown and overexpression studies with CHD1L to determine its role in Wnt/TCF-driven epithelial-to-mesenchymal transition (EMT). We performed high-throughput screening (HTS) to identify the first CHD1L inhibitors. The mechanism of action, antitumor efficacy, and drug-like properties of lead CHD1L inhibitors were determined using biochemical assays, cell models, tumor organoids, patient-derived tumor organoids, and in vivo pharmacokinetics and pharmacodynamics. Lead CHD1L inhibitors display potent in vitro antitumor activity by reversing TCF-driven EMT. The best lead CHD1L inhibitor possesses drug-like properties in pharmacokinetic/pharmacodynamic mouse models. This work validates CHD1L as a druggable target and establishes a novel therapeutic strategy for the treatment of colorectal cancer., (©2020 American Association for Cancer Research.)

Mesenchymal chondrosarcoma is a malignant neoplasm arising from cartilaginous bone or soft tissue. It is uncommon yet devastating. Our patient was a 21-year-old man who presented with pleuritic chest pain and weight loss. His chest radiograph showed left pleural effusion. His pleural effusion analysis was consistent with exudative pleural effusion. Tuberculosis workup was negative. Pleural fluid cytology did not yield malignant cells. Subsequently, his computed tomography of thorax showed left rib sclerotic lesion with soft tissue component. Biopsy of the soft tissue eventually confirmed the diagnosis of mesenchymal chondrosarcoma. He succumbed to his illness before the diagnosis was confirmed. We hope that through this case report, we are able to provide some insight into this rare condition.

Chronic pain affects a significant percentage of the United States population, and available pain medications like opioids have drawbacks that make long-term use untenable. Cannabinoids show promise in the management of pain, but long-term treatment of pain with cannabinoids has been challenging to implement in preclinical models. We developed a voluntary, gelatin oral self-administration paradigm that allowed male and female mice to consume ∆ 9 -tetrahydrocannabinol, cannabidiol, or morphine ad libitum. Mice stably consumed these gelatins over 3 weeks, with detectable serum levels. Using a real-time gelatin measurement system, we observed that mice consumed gelatin throughout the light and dark cycles, with animals consuming less THC-gelatin than the other gelatin groups. Consumption of all three gelatins reduced measures of allodynia in a chronic, neuropathic sciatic nerve injury model, but tolerance to morphine developed after 1 week while THC or CBD reduced allodynia over three weeks. Hyperalgesia gradually developed after sciatic nerve injury, and by the last day of testing, THC significantly reduced hyperalgesia, with a trend effect of CBD, and no effect of morphine. Mouse vocalizations were recorded throughout the experiment, and mice showed a large increase in ultrasonic, broadband clicks after sciatic nerve injury, which was reversed by THC, CBD, and morphine. This study demonstrates that mice voluntarily consume both cannabinoids and opioids via gelatin, and that cannabinoids provide long-term relief of chronic pain states. In addition, ultrasonic clicks may objectively represent mouse pain status and could be integrated into future pain models.

Metastasis is the cause of 90% of mortality in cancer patients. For metastatic colorectal cancer (mCRC), the standard-of-care drug therapies only palliate the symptoms but are ineffective, evidenced by a low survival rate of ∼11%. T-cell factor (TCF) transcription is a major driving force in CRC, and we have characterized it to be a master regulator of epithelial-mesenchymal transition (EMT). EMT transforms relatively benign epithelial tumor cells into quasi-mesenchymal or mesenchymal cells that possess cancer stem cell properties, promoting multidrug resistance and metastasis. We have identified topoisomerase IIα (TOP2A) as a DNA-binding factor required for TCF-transcription. Herein, we describe the design, synthesis, biological evaluation, and in vitro and in vivo pharmacokinetic analysis of TOP2A ATP-competitive inhibitors that prevent TCF-transcription and modulate or reverse EMT in mCRC. Unlike TOP2A poisons, ATP-competitive inhibitors do not damage DNA, potentially limiting adverse effects. This work demonstrates a new therapeutic strategy targeting TOP2A for the treatment of mCRC and potentially other types of cancers.

Next-generation sequencing of RNA extracted from a pumpkin plant with mosaic symptoms in Kenya identified the presence of a polerovirus sequence closely related to pepo aphid-borne yellows virus (PABYV). The near-complete polerovirus sequence comprised 5,810 nucleotides and contained seven putative open reading frames (ORFs) with a genome organisation typical of poleroviruses. BLASTp analysis of the translated sequences of ORFs 0, 1 and 2 revealed that their amino acid sequences differed by more than 10% from the corresponding protein sequences of other poleroviruses. These results suggest that this virus is a putative novel member of the genus Polerovirus, which has been provisionally named "pumpkin polerovirus" (PuPV).

Little information exists on the type and incidence of viruses infecting garlic ( Allium sativum L ) in Ethiopia. Attempts were made to identify the viruses using molecular techniques from 95 composite leaf samples collected from 44 farmers' fields and 51 germplasm accessions. Reverse transcription (RT-) PCR using genus and/or virus specific primers was used to amplify partial genome sequences of potyviruses, allexiviruses, carlaviruses and a tospovirus followed by sequencing of PCR products. Results indicated that ~73.7% of the samples are infected with at least one virus. Onion yellow dwarf virus (OYDV, genus Potyvirus , family Potyviridae ) is the most common virus detected followed by Garlic virus C (genus Allexivirus ) and Shallot latent virus (SLV, genus Carlavirus ). Other viruses detected at lower frequency include Garlic virus X and Garlic virus D (genus Allexivirus ), Leek yellow stripe virus (genus Potyvirus ) and Iris yellow spot virus (IYSV, genus Tospovirus ). Mixed infection of two or more viruses was detected in 65.7% of the samples. Phylogenetic analysis suggested that the different viruses may have been introduced to Ethiopia from Europe or Asia. This is the first report of Garlic virus X, Garlic virus D , IYSV and SLV in garlic in Ethiopia. The high incidence of OYDV and IYSV which cause severe yield loss alone or in mixed infection with allexiviruses and carlaviruses is a cause of concern to growers., (© The Author(s) 2019.)

Activation of κ opioid receptors (KORs) produces analgesia and aversion via distinct intracellular signaling pathways, but whether G protein-biased KOR agonists can be designed to have clinical utility will depend on a better understanding of the signaling mechanisms involved. We found that KOR activation produced conditioned place aversion and potentiated CPP for cocaine in male and female C57BL/6N mice. Consistent with this, males and females both showed arrestin-mediated increases in phospho-p38 MAPK following KOR activation. Unlike in males, however, KOR activation had inconsistent analgesic effects in females and KOR increased Gβγ-mediated ERK phosphorylation in males, but not females. KOR desensitization was not responsible for the lack of response in females because neither Grk3 nor Pdyn gene knock-out enhanced analgesia. Instead, responsiveness was estrous cycle dependent because KOR analgesia was evident during low estrogen phases of the cycle and in ovariectomized (OVX) females. Estradiol treatment of OVX females suppressed KOR-mediated analgesia, demonstrating that estradiol was sufficient to blunt Gβγ-mediated KOR signals. G protein-coupled receptor kinase 2 (GRK2) is known to regulate ERK activation, and we found that the inhibitory, phosphorylated form of GRK2 was significantly higher in intact females. GRK2/3 inhibition by CMPD101 increased KOR stimulation of phospho-ERK in females, decreased sex differences in KOR-mediated inhibition of dopamine release, and enhanced mu opioid receptor and KOR-mediated analgesia in females. In OVX females, estradiol increased the association between GRK2 and Gβγ. These studies suggest that estradiol, through increased phosphorylation of GRK2 and possible sequestration of Gβγ by GRK2, blunts G protein-mediated signals. SIGNIFICANCE STATEMENT Chronic pain disorders are more prevalent in females than males, but opioid receptor agonists show inconsistent analgesic efficacy in females. κ opioid receptor (KOR) agonists have been tested in clinical trials for treating pain disorders based on their analgesic properties and low addictive potential. However, the molecular mechanisms underlying sex differences in KOR actions were previously unknown. Our studies identify an intracellular mechanism involving estradiol regulation of G protein-coupled receptor kinase 2 that is responsible for sexually dimorphic analgesic responses following opioid receptor activation. Understanding this mechanism will be critical for developing effective nonaddictive opioid analgesics for use in women and characterizing sexually dimorphic effects in other inhibitory G protein-coupled receptor signaling responses., (Copyright © 2018 the authors 0270-6474/18/388031-13$15.00/0.)

The badnavirus taro bacilliform virus (TaBV) has been reported to infect taro (Colocasia esculenta L.) and other edible aroids in several South Pacific island countries, but there are no published reports from Australia. Using PCR and RCA, we identified and characterized an Australian TaBV isolate. A terminally redundant cloned copy of the TaBV genome was generated and shown to be infectious in taro following agro-inoculation. This is the first report of TaBV from Australia and also the first report of an infectious clone for this virus.

Taro ( Colocasia esculenta ) and tannia ( Xanthosoma sp.) are important root crops cultivated mainly by small-scale farmers in sub-Saharan Africa and the South Pacific. Viruses are known to be one of the most important constraints to production, with infections resulting in severe yield reduction. In 2014 and 2015, surveys were conducted in Ethiopia, Kenya, Tanzania and Uganda to determine the identity of viruses infecting taro in East Africa. Screening of 392 samples collected from the region using degenerate badnavirus primers revealed an incidence of 58-74% among the four countries surveyed, with sequence analysis identifying both Taro bacilliform virus (TaBV) and Taro bacilliform CH virus (TaBCHV). TaBCHV was identified from all four countries while TaBV was identified in all except Ethiopia. Full-length sequences from representative TaBV and TaBCHV isolates showed that the genome organization of TaBV isolates from East Africa was consistent with previous reports while TaBCHV isolates from East Africa were found to encode only four ORFs, distinct from a previous report from China. Phylogenetic analysis showed that all East African TaBV isolates form a single subgroup within known TaBV isolates, while TaBCHV isolates form at least two distinct subgroups. To the authors' knowledge, this is the first report describing the occurrence and genome organization of TaBV and TaBCHV isolates from East Africa and the first full-length sequence of the two viruses from tannia., (© 2018 The Authors.)

The dynorphin/κ-opioid receptor (KOR) system has been previously implicated in the regulation of cognition, but the neural circuitry and molecular mechanisms underlying KOR-mediated cognitive disruption are unknown. Here, we used an operational test of cognition involving timing and behavioral inhibition and found that systemic KOR activation impairs performance of male and female C57BL/6 mice in the differential reinforcement of low response rate (DRL) task. Systemic KOR antagonism also blocked stress-induced disruptions of DRL performance. KOR activation increased 'bursts' of incorrect responses in the DRL task and increased marble burying, suggesting that the observed disruptions in DRL performance may be attributed to KOR-induced increases in compulsive behavior. Local inactivation of KOR by injection of the long-acting antagonist nor-BNI in the ventral tegmental area (VTA), but not the infralimbic prefrontal cortex (PFC) or dorsal raphe nucleus (DRN), prevented disruption of DRL performance caused by systemic KOR activation. Cre-dependent genetic excision of KOR from dopaminergic, but not serotonergic neurons, also blocked KOR-mediated disruption of DRL performance. At the molecular level, we found that these disruptive effects did not require arrestin-dependent signaling, because neither global deletion of G-protein receptor kinase 3 (GRK3) nor cell-specific deletion of GRK3/arrestin-dependent p38α MAPK from dopamine neurons blocked KOR-mediated DRL disruptions. We then showed that nalfurafine, a clinically available G-biased KOR agonist, could also produce DRL disruptions. Together, these studies demonstrate that KOR activation in VTA dopamine neurons disrupts behavioral inhibition in a GRK3/arrestin-independent manner and suggests that KOR antagonists could be beneficial for decreasing stress-induced compulsive behaviors.