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This case report describes a rare case of nodal low grade serous pelvic neoplasia. Together with histological correlation, it illustrates previously undocumented cytomorphological features and also discusses important differential diagnosis and potential pitfalls for misdiagnosis. [ABSTRACT FROM AUTHOR]

Background/Objectives : Traditional paclitaxel therapy often results in significant side effects due to its non-specific targeting of cancer cells. Peptide aptamer-paclitaxel conjugates present a promising alternative by covalently attaching paclitaxel to a versatile peptide aptamer via a linker. Compared to antibody-paclitaxel conjugates, peptide aptamer-paclitaxel conjugates offer several advantages, including a smaller size, lower immunogenicity, improved tissue penetration, and easier engineering. Methods : This review provides an in-depth analysis of the multifunctional peptide aptamers in these conjugates, emphasizing their structural features, therapeutic efficacy, and challenges in clinical applications. Results : This analysis highlights the potential of peptide aptamer-paclitaxel conjugates as a novel and effective approach for targeted cancer therapy. By harnessing the unique properties of peptide aptamers, these conjugates demonstrate significant promise in improving drug delivery efficiency while reducing the adverse effects associated with traditional paclitaxel therapy. Conclusions : The incorporation of peptide aptamers into paclitaxel conjugates offers a promising pathway for developing more efficient and targeted cancer therapies. However, further research and clinical studies are essential to fully unlock the therapeutic potential of these innovative conjugates and enhance patient outcomes.

Background: In South Africa (SA), data on the incidence of thyroid cancer is limited. Papillary thyroid carcinoma is by far the most common malignancy in developed countries; however, a preponderance of follicular thyroid cancer in developing countries, despite iodized salt, has been observed. The aim of this study was to describe the national landscape of thyroid cancer in SA with reference to pathological subtypes, surgical outcomes, and treatments offered., Methods: A multi-institutional retrospective review of thyroid cancer patients operated on between January 2015 and December 2019 was performed. Public hospitals with associated academic institutions were included. Data were collected from theater registers, pathology, and radiology records. Statistical analysis was done to determine intergroup significance., Results: A total of 464 thyroid cancer cases from 13 centers across five SA provinces were identified. Most patients presented with a mass (67%). Ultrasound was performed in 82% of patients, and 16.3% underwent surgery without pre-operative cytology. Of the histologically confirmed thyroid cancers, 61.8% were papillary and 22.1% follicular thyroid cancer. There was a significant association between subtype and geographical area, and T-stage and operation performed. Surgical complication rates included hematoma in 1.8%, post-operative hypocalcemia in 28.7%, and recurrent laryngeal nerve injury in 3.5%., Conclusion: This first national review describes the landscape of thyroid cancer in SA, revealing considerable differences compared to international studies. It provides valuable insight into the unique South African experience with this disease. In addition, this study serves as an impetus towards a prospective national registry with real-world data informing contextualized guidelines., (© 2024 The Author(s). World Journal of Surgery published by John Wiley & Sons Ltd on behalf of International Society of Surgery/Société Internationale de Chirurgie (ISS/SIC).)

Pathogenic variants (mutations) and other molecular events involving subunits of the SWItch/Sucrose Non-Fermentable chromatin remodelling complex are common in a wide variety of malignancies. Many of these neoplasms are characterized by undifferentiated morphology. They arise at a variety of sites in the female genital tract but have rarely been reported in the uterine cervix. We report 2 primary cervical neoplasms arising in young women (ages 28 and 29 yr) exhibiting loss of nuclear immunoreactivity with SMARCB1 (INI1). In one case, which had a mixture of epithelioid and spindle cells, molecular studies revealed no SMARCB1 pathogenic variant, but showed a SPECCL1::NTRK 3 fusion, in keeping with an NTRK fusion sarcoma. The second case exhibited rhabdoid morphology and molecular testing confirmed a SMARCB1 pathogenic variant (c.425 T>G:p.(Leu142Ter) which, interpreted in conjunction with the morphology and immunohistochemistry, resulted in classification as a proximal-type epithelioid sarcoma. To our knowledge, this is the first reported cervical neoplasm exhibiting a SMARCB1 pathogenic variant and the first NTRK fusion sarcoma showing SMARCB1 protein loss. We discuss the diagnostic challenges and complexities of the molecular findings., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 by the International Society of Gynecological Pathologists.)

Thyroid gland vascular proliferations pose a challenge to pathologists, radiologists and surgeons. This is illustrated in the case of a 36-year-old woman who underwent a diagnostic thyroid lobectomy for a suspected follicular neoplasm according to cytology. Histological diagnosis confirmed a follicular adenoma as well as a cavernous haemangioma or venous malformation., Contribution: Thyroid vascular lesions are rare. Evolving nomenclature and application of the International Society for the Study of Vascular Anomalies classification are discussed. Pertinent radiological clues are highlighted to pre-empt the diagnosis and avoid potential surgical complications., Competing Interests: The authors declare that they have no financial or personal relationship(s) that may have inappropriately influenced them in writing this article., (© 2024. The Authors.)

As an important immune stimulator and modulator, IFNγ is crucial for gut homeostasis and its dysregulation links to diverse colon pathologies, such as colitis and colorectal cancer (CRC). Here, we demonstrated that the epigenetic regulator, CBX3 (also known as HP1γ) antagonizes IFNγ signaling in the colon epithelium by transcriptionally repressing two critical IFNγ-responsive genes: STAT1 and CD274 (encoding Programmed death-ligand 1, PD-L1). Accordingly, CBX3 deletion resulted in chronic mouse colon inflammation, accompanied by upregulated STAT1 and CD274 expressions. Chromatin immunoprecipitation indicated that CBX3 tethers to STAT1 and CD274 promoters to inhibit their expression. Reversely, IFNγ significantly reduces CBX3 binding to these promoters and primes gene expression. This antagonist effect between CBX3 and IFNγ on STAT1/PD-L1 expression was also observed in CRC. Strikingly, CBX3 deletion heightened CRC cells sensitivity to IFNγ, which ultimately enhanced their chemosensitivity under IFNγ stimulation in vitro with CRC cells and in vivo with a syngeneic mouse tumor model. Overall, this work reveals that by negatively tuning IFNγ-stimulated immune genes' transcription, CBX3 participates in modulating colon inflammatory response and CRC chemo-resistance., (© 2024. The Author(s).)

Osteogenesis imperfecta (OI) is a rare genetic disease characterized by bone fragility and bone formation. Sclerostin could negatively regulate bone formation by antagonizing the Wnt signal pathway, whereas it imposes severe cardiac ischemic events in clinic. Our team has screened an aptamer that could promote bone anabolic potential without cardiovascular risk. However, the affinity of the aptamer is lower and needs to be improved. In the study, hydrophobic quinoline molecule with unique orientations (seven subtypes) were incorporated into key sites of a bone anabolic aptamer against sclerostin to form a modified aptamer library. Among all the quinoline modifications, 5-quinoline modification could shape the molecular recognition of modified aptamers to sclerostin to facilitate enhancing its binding to sclerostin toward the highest affinity by interacting with newly participated binding sites in sclerostin. Further, 5-quinoline modification could facilitate the modified aptamer attenuating the suppressed effect of the transfected sclerostin on both Wnt signaling and bone formation marker expression levels in vitro , promoting bone anabolism in OI mice ( Col1a2 +/G610C ). The proposed quinoline-oriented modification strategy could shape the molecular recognition of modified aptamers to proteins to facilitate enhancing its binding affinity and therapeutic potency., 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., (© 2024 The Author(s).)

Aims: NTRK-rearranged sarcomas of the female genital tract mainly occur in the uterus (more commonly cervix than corpus) and are characterized by a "fibrosarcoma-like" morphology and NTRK gene rearrangements. These neoplasms may exhibit histological overlap with other entities and can present diagnostic difficulties without molecular confirmation. Pan-TRK immunohistochemistry was developed to identify tumours harbouring NTRK rearrangements. The aim of this study was to characterize pan-TRK immunohistochemical expression in a large cohort of gynaecological mesenchymal neoplasms and investigate the utility of pan-TRK immunohistochemistry to distinguish NTRK-rearranged sarcoma from its mimics., Methods and Results: A total of 473 gynaecological mesenchymal tumours (461 without known NTRK fusions and 12 NTRK-rearranged sarcomas) were selected. Pan-TRK immunohistochemistry (EPR17341, Abcam) was performed on whole tissue sections and tissue microarrays. Molecular interrogation of pan-TRK positive tumours was performed by RNA sequencing or fluorescence in situ hybridization (FISH). Of the 12 NTRK-rearranged sarcomas, 11 (92%) exhibited diffuse (≥70%) cytoplasmic pan-TRK staining with moderate/marked intensity, while the other was negative. Eleven (2.4%) additional tumours also exhibited pan-TRK immunohistochemical expression: three low-grade endometrial stromal sarcomas, seven high-grade endometrial stromal sarcomas, and an undifferentiated uterine sarcoma. Molecular confirmation of the absence of NTRK rearrangements was possible in nine of these tumours. Of these nine neoplasms, seven exhibited focal/multifocal (<70%) pan-TRK cytoplasmic staining with weak/moderate intensity., Conclusion: Even though pan-TRK immunohistochemical expression is not entirely sensitive or specific for NTRK-rearranged sarcomas, these neoplasms tend to exhibit diffuse staining of moderate/strong intensity, unlike its mimics. Pan-TRK should be performed in monomorphic uterine (corpus and cervix) spindle cell neoplasms that are negative for smooth muscle markers and hormone receptors and positive for CD34 and/ or S100. Ultimately, the diagnosis requires molecular confirmation., (© 2023 John Wiley & Sons Ltd.)

Introduction: The 6 categories of the Bethesda System for Reporting Thyroid Cytology (TBSRTC) with associated risk of malignancy (ROM) provide evidence-based clinical management guidelines. This study aimed to determine the ROM and accuracy of FNAB in South Africa (SA)., Methods: Thyroid specimens from 3 pathology laboratories registered between January 2015 and December 2019 were considered for inclusion. ROM was obtained per TBSRTC category by cytohistological correlation and dividing the total number of specimens with malignant histology by the total number of cases operated. Accuracy was calculated based on the Bethesda category and eventual malignant histology., Results: Seventeen thousand seven hundred and seventy-three histology and 4,791 cytology cases were identified. Of the 4,791 cytology cases, 931 (19%) underwent surgery. More than a third (333, 35.8%) of cases were confirmed as malignant following histological assessment, with the majority being benign (584, 62.7%). The ROM for the nondiagnostic and benign categories was 24.3% and 20.5%. The highest ROM was for category VI (91.5%), followed by categories V (69.5%), IV (51.9%), and III (38.8%). Thyroid FNAB had a sensitivity of 73%, specificity of 74%, and overall accuracy of 74%., Conclusion: Bethesda categories II and IV have a relatively higher ROM in SA compared to findings from other developed countries. The diagnostic accuracy of thyroid FNAB in SA and the high rate of nondiagnostic diagnoses (38%) require further investigation. A national thyroid registry could provide location-specific data to aid the implementation of appropriate local policies and national guidelines for practicing thyroid surgeons., (© 2024 S. Karger AG, Basel.)

Introduction: Microsecretory adenocarcinoma (MSA) is a novel entity defined by distinctive histology, a specific immunophenotype, and unique molecular fusion MEF2C::SS18. It occurs mainly in intra-oral minor salivary glands and the skin, with only one reported case affecting the parotid gland. To the best of our knowledge, no cytomorphological features of MSA have been published to date. We report the first case of fine-needle aspiration biopsy (FNAB) cytology of MSA diagnosed in the parotid gland., Case Presentation: A 48-year-old man presented with a 3.5 × 2.5-cm parotid mass. FNAB of the tumour revealed a cellular smear comprising a predominantly epithelial cell population showing luminal differentiation with secretory features and a distinctive background matrix with both myxoid and mucinous qualities. Scattered, but conspicuous multinucleated giant cells were present, a feature not commonly observed in salivary gland aspirates. Histology of the excised tumour revealed classic features of MSA with supportive immunohistochemistry and SS18 break apart fusion detected by fluorescence in situ hybridisation (FISH). Next-generation sequencing confirmed a MEF2C::SS18 gene fusion., Conclusion: MSA is a rare neoplasm and should be considered in the cytological differential diagnosis of low-grade salivary gland neoplasms. Its unique cytomorphological features should raise the possibility of MSA in salivary gland FNABs. The diagnosis can be established on cellular cell block preparations using immunohistochemistry and FISH or PCR., (© 2024 S. Karger AG, Basel.)

Background & Rationale: Malaria is a major health problem in Benin where it is the main cause of morbidity and mortality, particularly among children under 5 and pregnant women. Although the vast majority of malaria cases occurs in rural and agricultural areas and are often associated with development projects, very few interventions target the agro-ecosystem. In Benin, irrigated rice growing is expanding to meet the increasing demand of the population. However, continuous flooding and tillage systems induce the development and proliferation of malaria and other diseases vectors. Intermittent flooding of rice plots and minimal tillage can reduce significantly the proliferation of mosquitoes including Anopheles in rice fields. However, the dissemination and implementation of these agricultural practices require community-wide action for greater effectiveness. As part of strengthening the capacity of farming communities in the fight against malaria vectors, the "Farmer Field School" appears to be an innovative approach. This learning by doing method promotes interactions between groups of producers to disseminate proven technologies. This study aims to disseminate among rice producers the agricultural practices of intermittent flooding and minimal tillage, likely to reduce the proliferation of malaria vectors in the rice fields., Materials & Methods: This study was carried out in the rice-growing perimeter of Malanville, Benin (11° 52' 5" North, 3° 22' 59" East) which covers an area of 516 hectares. Farmer Field Schools were set up after a basic survey at producer level. This survey was carried out through in-depth interview, focus group discussions and direct field observation with producers. Focus groups discussions and interviews made it possible to understand the perception of rice farmers on the link between rice production and the transmission of malaria. In order to disseminate new agricultural practices such as intermittent flooding and minimal tillage among producers, twelve plots have been set up. Farmer Field Schools were monitored weekly with rice producers accompanied by a facilitator and a medical entomologist (learning facilitator or moderator) helping the farmers with the collection and identification of mosquito larvae. According to the different stages of rice development (transplanting, tillering, maturation), the mosquito larvae were collected in the test and control plots from 10 a.m. to 2 p.m. by the dipping method. Then the water in the test compartments (intermittent flooding) was emptied. A cycle of 7 days of flooding and 2 days of drying was carried out for intermittent flooding. Mosquito larvae were identified morphologically using the identification key and Anopheles genus larvae were isolated in plastic cups. The impacts of intermittent flooding and minimum tillage in reducing breeding sites and larval densities were established by determining and comparing the larval densities of mosquitoes and of Anopheles between the test and control plots., Results: Direct observations in the field allowed to identify three tillage systems, which include the use of tiller (28%), plow (66%) and hoe (6%) on the rice field. Continuous flooding was the only irrigation system used by farmers. The water used for irrigation comes either from boreholes installed individually or from the Niger River. The volume of water used varies with the seasons, the size of the farms and the variety of rice grown. Farmers observe that the nuisance of mosquitoes increases during the rice production period with an outbreak of malaria cases, especially among children, which leads to crowds in health centers. The preventive measures against malaria among farmers are the use of impregnated mosquito nets distributed free of charge by the national program against malaria, and of insecticide bombs or spirals. Considering the development stages of the rice, the larval densities varied according to the treatments. Overall, minimal tillage applied to intermittent flooding significantly reduced the density of mosquito larvae of all species. The reduction rates were 10.5, 5.4 and 2.5 during transplanting, tillering and maturation, respectively. Considering only the Anopheles larvae, minimal tillage applied to intermittent flooding reduced their density by 16, 5.5 and 4 respectively during transplanting, tillering and maturation., Discussion/conclusion: The rice-growing area of Malanville has many favorable conditions for rice production, including the presence of water supply sources such as the Niger River located near the rice field and numerous boreholes. The availability of water pockets for mosquito breeding during irrigation appeared to contribute to the extension of malaria transmission. The present study showed that the intermittent flooding coupled with minimal tillage could reduce the proliferation of malaria vectors. The results suggested that with technical support to farmers through the "Farmer Field School", the malaria incidence could be reduced in the farming community., (Copyright © 2023 SFMTSI.)

Background: Achieving viral suppression (VS) for persons living with HIV is key to reaching epidemic control. We assessed the prevalence of VS and the frequency of HIV drug resistance mutations (HIVDRM) among children and adolescents living with HIV (CALHIV) in the Southern Highland zone of Tanzania., Methods: From 2019 to 2021, we enrolled CALHIV aged 1-19 years on ART for >6 months in a cross-sectional study. Participants had viral load (VL) testing; those with VL ≥ 1000 copies/mL underwent HIVDRM testing. VS (<1000 copies/mL) prevalence estimates were calculated and robust Poisson regression was used to estimate prevalence ratios (PRs) and 95% confidence intervals (CIs) for associations with potential predictors of VS., Results: Of 707 participants, 595 had VS (PR: 0.84, 95% CI: 0.81-0.87). Use of an integrase strand transfer inhibitor-containing regimen (aPR 1.15, 95% CI: 0.99-1.34), age 5-9 years (aPR 1.16, 95% CI: 1.07-1.26), and seeking care at a referral center (aPR 1.12, 95% CI: 1.04-1.21) were associated with VS. Factors inversely associated with VS included having one (aPR 0.82, 95% CI: 0.72-0.92) or two or more (aPR 0.79, 95% CI: 0.66-0.94) referrals for adherence counselling, and self-reporting missing one to two (aPR 0.88, 95% CI: 0.78-0.99) or three or more (aPR 0.77, 95% CI: 0.63-0.92) doses of ART in the past month. Of 74 participants with PRRT and INT sequencing done, 60 (81.1%) had HIVDRMs at the following frequencies: 71.6%, 67.6%, 1.4%, and 4.1% for major NNRTI, NRTI, PI, and INSTI respectively., Conclusions: Higher rates of VS were observed in this cohort, and HIVDRMs were common in those without VS. This evidence supports ART optimization using dolutegravir-based regimens. However, better strategies to improve adherence are needed., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society.)

The authors highlight the important contribution of rapid on-site evaluation by the cytopathologist of a pharyngoesophageal diverticulum in a mass initially interpreted clinically as thyroidal in origin. They discuss pitfalls in avoiding interpretive diagnostic error and inappropriate thyroid Bethesda reporting., (© 2022 The Authors. Cytopathology published by John Wiley & Sons Ltd.)

Epstein-Barr virus (EBV)-positive mucocutaneous ulcer (EBVMCU) is a newly described lymphoproliferative lesion characterized by the proliferation of EBV-positive atypical B cells in a variable inflammatory background associated with mucosal or cutaneous ulcers. Commonly involved sites include the oropharyngeal tract, skin, and gastrointestinal tract, with emerging reports describing EBVMCU of genitalia. To date, no lesions have been described of the uterine cervix. Herein, we report the first cervical EBVMCU incidentally discovered at large loop excision of the transformation zone performed for treating human papillomavirus induced high-grade squamous intraepithelial lesion. The patient was a 35-yr-old, human immunodeficiency virus-positive woman with a history of pulmonary tuberculosis. Histologic and immunohistochemical findings showed classic Hodgkin lymphoma-like features. Systemic lymphoproliferative disease was excluded by appropriate clinical and imaging modalities. This case report highlights the prototypical histologic features of cervical EBVMCU. We emphasize the importance of clinicopathologic correlation to avoid overtreatment of a lesion that can otherwise meet histologic criteria for a lymphoma. Clinicians and pathologists should familiarize themselves with this entity, as this indolent, pseudomaligant lesion typically occurs in immunocompromised patients and spontaneously regresses when the cause for the immunosuppression is addressed., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 by the International Society of Gynecological Pathologists.)

Although global assessments of the initial impacts of the coronavirus disease (COVID-19) have focused on income, jobs, and health conditions, this study constitutes one of the first studies that assessed the impact of COVID-19 on food security in DRC and established the short-term implications of the COVID-19 outbreak on rural households' food security in DRC. In addition, the study recommendations contributed to shaping government interventions toward the pandemic in the Country. The study used data from four western provinces of the country on 1339 households. Our results show that 80 % of households experienced an increase in food prices, 61 % a noticeable decrease in the availability of food, and 54 % a decrease in their dietary diversity. Due to changes in food availability, dietary diversity, and food accessibility imposed by the COVID-19 outbreak, >70 % of households experienced either a decrease in the consumption of meat, milk, fish, and cereals or an increase in their consumption of traditional vegetables. In addition, COVID-19 significantly affected food security dimensions in larger households, households with a greater number of members aged 35 years and above, households headed by women, households where members participate in associations or cooperatives, households that depend on crop sales as the major source of income, and in poorer households. These findings highlight the significant implications of the COVID-19 outbreak on household food security in western DRC and underscore the need for emergency interventions to strengthen the resilience of rural people and accelerate their recovery and other long-term measures toward sustainable and inclusive development., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

We report a unique primary cervical neoplasm in a 44-yr-old woman which we believe, based on the morphology and immunophenotype, represents an extremely unusual small cell variant of paraganglioma. This represents the first report of a primary cervical paraganglioma. Following chemoradiation treatment, the tumor underwent malignant transformation into an S100 and SOX10 positive sarcoma, morphologically and immunohistochemically resembling a malignant peripheral nerve sheath tumor, which we believe represents a sarcoma derived from the sustentacular cells of the paraganglioma. Mutational analysis detected a nonsense mutation of NF1 gene in the sarcoma. This further supports the diagnosis as both somatic and germline NF1 mutations have been associated with paragangliomas and malignant peripheral nerve sheath tumors. Targeted RNA sequencing (ARCHER, expanded sarcoma panel) covering many known genes implicated in sarcoma development, did not reveal any other molecular alteration (fusion or internal tandem duplication)., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 by the International Society of Gynecological Pathologists.)

Pancreatic cancer (PC) is one of the most lethal cancers with an almost 10% 5-year survival rate. Because PC is implicated in high heterogeneity, desmoplastic tumor-microenvironment, and inefficient drug-penetration, the chemotherapeutic strategy currently recommended for the treatment of PC has limited clinical benefit. Nucleic acid-based targeting therapies have become strong competitors in the realm of drug discovery and targeted therapy. A vast evidence has demonstrated that antibody-based or alternatively aptamer-based strategy largely contributed to the elevated drug accumulation in tumors with reduced systematic cytotoxicity. This review describes the advanced progress of antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), microRNAs (miRNAs), messenger RNA (mRNAs), and aptamer-drug conjugates (ApDCs) in the treatment of PC, revealing the bright application and development direction in PC therapy., Competing Interests: Authors FL, YM, AL, GZ were employed by the “Institute of Precision Medicine and Innovative Drug Discovery”. The remaining 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 Dai, Abdullah, Wu, Li, Ma, Lu and Zhang.)

Background: Thyroid nodules are common and mostly benign. Inadequate sampling generally occurs in 13 - 17% of thyroid fine-needle aspiration biopsies (FNABs), but the proportion was found to be as high as 45% on evaluating 100 ultrasound (US)-guided FNABs in a previous unpublished audit at Tygerberg Hospital, Cape Town, South Africa (SA)., Objectives: Primary aim: To determine the diagnostic yield of US-guided thyroid biopsy after implementing changes to existing practices, involving the creation of a specialised clinic and applying protocols for referral and FNAB. Secondary aim: To compare the results with other centres in SA., Methods: A retrospective audit of 178 thyroid biopsies was conducted. All US-guided thyroid biopsies performed in the specialised clinic between January 2017 and July 2018 were included. Data were analysed using descriptive statistics., Results: The 178 nodules were biopsied in 159 patients. The mean age was 53.7 years, with a gender ratio of 9.6:1 (female/male). A reduction in non-diagnostic biopsies was noted compared with the historical cohort (45% v. 32.6%). Sixty-one nodules (34.3%) had previously been biopsied with inadequate cytology results. When repeat biopsies were excluded, only 16.2% (n=19) were classified as insufficient., Conclusions: These findings illustrate the importance of the multidisciplinary approach and standardisation of the US-guided biopsy procedure and the value of consistency and quality control in a health system. While nodular thyroid disease is common and FNAB is relatively simple, early referral to a central specialised unit to minimise the incidence of inadequate FNAB should be considered.

Objectives: Lead exposure seriously impairs male reproductive function. The protective capacity of Pedalium murex leafy stem and fruit aqueous extracts against lead testicular toxicity is evaluated to find herbals drugs able to improve semen quality., Methods: Phytochemical screening were performed according to classical methods. Twenty four male rats were divided into four groups of six rats each and received the following treatments via oral route: distilled water; 0.2% lead acetate in drinking water; 0.2% lead acetate in drinking water with 400 mg/kg P. murex aqueous leafy stem extract; 0.2% leaded water with 400 mg/kg P. murex aqueous fruit extract. Treatments were administered for 70 days. Body and reproductive organs weights, sperm parameters and testicular histological sections of each group were examined., Results: Flavonoids, tannins, coumarins, alkaloids, and lignans were found in both extracts. Lead intoxication reduced sperm motility and count but increased the percentage of morphologically abnormal sperms. The germinal epithelium of seminiferous tubules histoarchitecture was disorganized by lead. The leafy stem extract was effective in reducing lead induced testicular disruption whereas fruit has not shown any beneficial effect., Conclusions: P. murex leafy stem aqueous extract is effective against semen alterations caused by lead., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Background: The COVID-19 pandemic has disrupted cancer diagnostic services. A decline in the number of new cancers being diagnosed over a relatively short term implies a delay in diagnosis and subsequent treatment. This delay is expected to have a negative effect on cancerrelated morbidity and mortality. The impact of the pandemic on the number of new cancer diagnoses in our setting is unknown., Objectives: To assess the impact of COVID-19 on the number of new cancers diagnosed at our institution in the first 3 months following the implementation of lockdown restrictions, by focusing on common non-cutaneous cancers., Methods: A retrospective laboratory-based audit was performed at a large anatomical pathology laboratory in Western Cape Province, South Africa. The numbers of new diagnoses for six common cancers (breast, prostate, cervix, large bowel, oesophagus and stomach) from 1 April 2020 to 30 June 2020 were compared with the corresponding period in 2019., Results: Histopathological diagnoses for the six cancers combined decreased by 192 (-36.2%), from 531 new cases in the 2019 study period to 339 in the corresponding period in 2020. Substantial declines were seen for prostate (-58.2%), oesophageal (-44.1%), breast (-32.9%), gastric (-32.6%) and colorectal cancer (-29.2%). The smallest decline was seen in cervical cancer (-7%). New breast cancers diagnosed by cytopathology declined by 61.1%., Conclusions: The first wave of the COVID-19 pandemic and the associated response resulted in a substantial decline in the number of new cancer diagnoses, implying a delay in diagnosis. Cancer-related morbidity and mortality is expected to rise as a result, with the greatest increase in mortality expected from breast and colorectal cancer.

Background: Plant medicine is the oldest form of health care known to mankind; hence, studies on their safety for use are essential for the control of adverse drug effects. In Benin, Caesalpinia bonduc is one of many medicinal plants used as aphrodisiac, and for treatment of various ailments including prostatic hyperplasia. Despite its numerous ethnomedicinal benefits, toxicological information associated with its chronic use is currently limited., Objective: The present study therefore assessed the toxicity of an ethanolic root extract of Caesalpinia bonduc in Wistar rats., Methods: Caesalpinia bonduc root extract was administered by oral gavage at doses of 31.25, 125, and 500 mg/kg/day for 90 days to male Wistar rats, after which body weight changes, food consumption, urinary parameters, hematological and blood biochemical parameters, organ weights changes, gross pathology, and histopathology of vital organs were assessed., Results: There were no death or abnormal clinical signs, no significant changes in body weight gain or urinary parameters, and no changes in necropsy and histopathology findings of vital organs associated with extract treatment. However, some indices such as erythrocytes, total cholesterol, and aspartate amino transferase increased in rats treated with high doses of the extract, as well as relative weight of testes, followed by a decrease in food intake and prostate relative weight., Conclusion: The results indicate that an ethanolic root extract of Caesalpinia bonduc does not cause significant adverse effects and suggest its tolerability up to 500 mg/kg for daily administration of 90 days., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2021 Mariette Sindete et al.)

To adapt is to survive. However, sub-Saharan Africa, although highly dependent on agriculture, is vulnerable, most affected, with low-adaptive capacity. Luckily, the region is blessed with inherent adaptation-related strengths that are within reach, to counteract uncertainty in climatic patterns which are expected to continue well into the future. One such strength is a bimodal rainfall pattern that avails the 'hidden' multiple season-cropping systems that have the potential to produce four types of crops in a single plot in a single year: short-rains crops, long-rains crops, permanent crops and fruit crops. Despite burgeoning literature on adaptation, the impact of multiple season-cropping systems has not been adequately investigated. This study applies a novel approach to measure its impact on productivity of more than 10,000 smallholder plots using an endogenous switching regression framework. The study finds that plots that adopt multiple season-cropping systems produce higher quantities, earn more crop revenue, and are less likely to be affected by rainfall variability in comparison to plots that engage in single season-cropping systems. As the fight against climate change continues, there is need to move the needle on adaptation and consider strategies that are within reach. The multiple season-cropping systems provide this opportunity and emphasises the benefit of engaging in agriculture throughout the year and producing long-rains, short rains, permanent and fruits crops., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: This study aims to determine the diagnostic utility of the International Academy of Cytology (IAC) Yokohama System for reporting breast cytopathology in lesions of the male breast., Study Design: Fine-needle aspiration biopsy (FNAB) reports between 2015 and 2019 were retrospectively recategorized according to the 5-tiered IAC Yokohama Reporting System. Our database yielded a total of 1,532 FNAB reports from breast lesions, obtained from 1,350 male patients. The risk of malignancy (ROM) and diagnostic performance of FNAB were determined using follow-up histopathological diagnosis and/or clinical follow-up, where available, for each category., Results: The category distribution were as follows: inadequate, 40%; benign, 57%; atypical, 0.6%; suspicious for malignancy, 0.7%; and malignant, 1.6%. The ROM in each category was nondiagnostic, 11%; benign, 3%; atypical, 28%; suspicious for malignancy, 56%; and malignant, 100%. The sensitivity, specificity, positive predictive value, and negative predictive value were recorded as 63, 100, 100, and 84.6% respectively, when only malignant cases were considered as positive tests., Conclusion: This study validates the IAC Yokohama System for reporting male breast cytopathology. In accordance with the aim of the Yokohama System to establish best practice guidelines for reporting breast cytopathology, this comprehensive scheme facilitates comparisons between local and international institutions. The ROM acts as an internal audit for quality assurance within one's own laboratory and provides guidance for clinical management. It highlights inefficiencies such as high inadequacy rates for category 1 and also features strengths with impressive specificity for categories 4 and 5., (© 2020 S. Karger AG, Basel.)

Background: Irrigation systems have been identified as one of the factors promoting malaria disease around agricultural farms in sub-Saharan Africa. However, if improved water management strategy is adopted during rice cultivation, it may help to reduce malaria cases among human population living around rice fields. This study aimed to assess the impact of the different irrigation practices on malaria transmission, as well as to evaluate the water management system that will best mitigate malaria transmission in Malanville, Benin., Methods: Knowledge, Attitude and Practice (KAP) study was conducted on 104 households staying on and around the rice fields in Malanville. The study focused on the frequency of mosquito bites and preventive measures against malaria as well as soil preparation and rice planting methods. Mosquito larvae density was assessed in different water management system: continuous flooding (CF) or intermittent flooding (IF), deep tillage (DT) or minimal tillage (MT) and normal levelling (NL) or abnormal levelling (AL) in an experimental hut set-up. Larvae were collected using dipping methods and their density was determined., Results: Three tillage systems, which include the use of tiller, plow and hoe, were identified on the rice field. Continuous flooding was the only irrigation system used by farmers. Retrospective data from Malanville Health Centre revealed higher malaria cases during rice production season, which was also confirmed by field participants. The density of Anopheles larvae was reduced by 80.8%, 30.8% and 40.7% (P = 0.000) during transplanting, tillering and maturation periods, respectively with intermittent flooding compared to continuous flooding. In addition, a clear reduction of larva density was observed with both intermittent flooding systems applied to minimal tillage (MT + IF + NL) and intermittent flooding applied to deep tillage (DT + IF + AL), showing that intermittent flooding could reduce the abundance of malaria vector in rice fields., Conclusion: Recommending intermittent flooding technology for rice cultivation may not only be useful for water management but could also be an intentional strategy to control mosquitoes vector-borne diseases around rice farms.

Background: Clinical trials of interventions for preventing malaria in pregnancy often use measures of malaria at delivery as their primary outcome. Although the objective of these interventions is to improve birth outcomes, data on associations between different measures of malaria at delivery and adverse birth outcomes are limited., Methods: Data came from 637 Ugandan women enrolled in a randomized controlled trial of intermittent preventive treatment of malaria in pregnancy. Malaria at delivery was detected using peripheral and placental blood microscopy, placental blood loop-mediated isothermal amplification (LAMP), and placental histopathology. Multivariate analyses were used to estimate associations between measures of malaria at delivery and risks of low birth weight (LBW), small for gestational age (SGA), and preterm birth (PTB)., Results: Detection of malaria parasites by microscopy or LAMP was not associated with adverse birth outcomes. Presence of malaria pigment detected by histopathology in ≥30% of high-powered fields was strongly associated with LBW (adjusted risk ratio [aRR] = 3.42, P = .02) and SGA (aRR = 4.24, P < .001) but not PTB (aRR = 0.88, P = .87)., Conclusions: A semiquantitative classification system based on histopathologically detected malaria pigment provided the best surrogate measure of adverse birth outcomes in a high-transmission setting and should be considered for use in malaria in pregnancy intervention studies., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

We present an unusual case of syphilitic pancreatitis and ascending aortitis in a 41-year-old HIV-negative male patient presenting to a tertiary institution with obstructive jaundice. After a battery of investigations that included computed tomography (CT) and 18F-labelled fluorodeoxyglucose positron emission tomography/CT (18F-FDG PET/CT) imaging, syphilis serology and histology, a diagnosis of tertiary syphilis was made. The patient responded favourably to antibiotics, with resolution of all lesions on FDG PET/CT 13 weeks after initiation of therapy. Even though tertiary syphilis is a rare entity, it should be earmarked as a mimicker of other pathological conditions, including, in this case, primary pancreatic malignancy.

Termites are widely used as a food resource, particularly in Africa and Asia. Markets for insects as food are also expanding worldwide. To inform the development of insect-based foods, we analysed selected minerals (Fe-Mn-Zn-Cu-Mg) in wild-harvested and commercially available termites. Mineral values were compared to selected commercially available insects. Alate termites, of the genera Macrotermes and Odontotermes, showed remarkably high manganese (Mn) content (292-515 mg/100 gdw), roughly 50-100 times the concentrations detected in other insects. Other mineral elements occur at moderate concentrations in all insects examined. On further examination, the Mn is located primarily in the abdomens of the Macrotermes subhyalinus; with scanning electron microscopy revealing small spherical structures highly enriched for Mn. We identify the fungus comb, of Macrotermes subhyanus, as a potential biological source of the high Mn concentrations. Consuming even small quantities of termite alates could exceed current upper recommended intakes for Mn in both adults and children. Given the widespread use of termites as food, a better understanding the sources, distribution and bio-availability of these high Mn concentrations in termite alates is needed.

Background: Placental malaria is a major cause of adverse birth outcomes. However, data are limited on the relationships between longitudinal measures of parasitemia during pregnancy and placental malaria., Methods: Data came from 637 women enrolled in a randomized controlled trial of intermittent preventive treatment of malaria in pregnancy (IPTp) from Uganda. Plasmodium falciparum parasitemia was assessed using microscopy and ultrasensitive quantitative PCR at intervals of 28 days from 12 to 20 weeks gestation through delivery. Multivariate analysis was used to measure associations between characteristics of parasitemia during pregnancy and the risk of placental malaria based on histopathology., Results: Overall risk of placental malaria was 44.6%. None of the 34 women without parasitemia detected during pregnancy had evidence of placental malaria. Increasing proportion of interval assessments with parasitemia and higher parasite densities were independently associated with an increased risk of placental malaria. Higher gravidity and more effective IPTp were associated with a decreased risk of placental malaria. Women with parasitemia only detected before the third trimester still had an increased risk of placental malaria., Conclusions: The frequency, density, and timing of parasitemia are all important risk factors for placental malaria. Interventions should target the prevention of all levels of parasitemia throughout pregnancy., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

We propose a novel laboratory experiment to document the pressure to share income within social networks in Africa. We find that the redistributive pressure exerted via the possibility of receiving a claim increases altruism, while the possibility of hiding from such claim reduces it. Our results indicate that sharing norms are crucial drivers of giving to other members of the network. We also find that pressure to share has a detrimental effect on the undertaking of profitable but risky investments., Competing Interests: The authors have declared that no competing interests exist.

Background: Preterm birth (PTB) is a leading cause of neonatal mortality and longer-term morbidity. Acute chorioamnionitis (ACA) is a common cause of PTB, however, there are limited data on the prevalence of ACA and its association with PTB in resource limited settings., Methods: Data and samples came from a clinical trial evaluating novel strategies for the prevention of malaria in HIV infected pregnant women in Uganda. Women were enrolled between 12-28 weeks of gestation and followed through delivery. For each placenta delivered, three placental tissue types (membrane roll, umbilical cord and chorionic plate/villous parenchyma) were collected. Slides were assessed for diagnosis of maternal and fetal ACA by microscopic evaluation of neutrophilic infiltration using a standardized grading scale. The primary outcomes were PTB (<37 weeks), low birth weight (LBW, <2500 grams), and small-for-gestational age (SGA, birth weight <10th percentile for age). Univariate and multivariate logistic regression were used to estimate associations between 1) maternal characteristics (age, education, wealth, gravidity, gestational age at enrollment, placental malaria, anti-malarial prophylaxis treatment regimen, HIV disease parameters) and ACA, and 2) associations between ACA and adverse birth outcomes., Findings: A total of 193 placentas were included in the analysis. The prevalence of maternal and fetal ACA was 44.5% and 28.0%, respectively. HIV infected women between 28-43 years of age had a higher risk of maternal ACA compared to those between 17-21 years of age (50.9% vs. 19.1%; aOR = 4.00 (1.10-14.5), p = 0.04) and the diagnosis of severe maternal ACA was associated with a significantly higher risk of PTB (28.6% vs. 6.0%; aOR = 6.04 (1.87-19.5), p = 0.003), LBW (33.3% vs. 9.4%; aOR = 4.86 (1.65-14.3); p = 0.004), and SGA (28.6% vs. 10.1%; aOR = 3.70 (1.20-11.4), p = 0.02). No maternal characteristics were significantly associated with fetal ACA and the diagnosis of fetal ACA was not associated with adverse birth outcomes., Conclusions: Histological evidence of severe maternal ACA was associated with an increased risk of PTB, LBW, and SGA in HIV infected, pregnant Ugandan women., Competing Interests: The authors have declared that no competing interests exist.

In this article, we used an artificial DNA base to manipulate the formation of DNA nanoflowers (NFs) to easily control their sizes and functionalities. Nanoflowers have been reported as the noncanonical self-assembly of multifunctional DNA nanostructures, assembled from long DNA building blocks generated by rolling circle replication (RCR). They could be incorporated with myriad functional moieties. However, the efficacy of these DNA NFs as potential nanocarriers delivering cargo in biomedicine is limited by the bioavailability and therapeutic efficacy of their cargo. Here we report the incorporation of metal-containing artificial analogues into DNA strands to control the size and the functions of NFs. We have engineered bioinspired, size-controllable, self-degradable cancer-targeting DNA nanoflowers (Sgc8-NFs-Fc) via the incorporation of an artificial sandwich base. More specifically, the introduction of a ferrocene base not only resulted in the size controllability of Sgc8-NFs-Fc from 1000 to 50 nm but also endowed Sgc8-NFs-Fc with self-degradability in the presence of H 2 O 2 via Fenton's reaction. In vitro experiments confirmed that Sgc8-NFs-Fc/Dox could be selectively taken up by protein tyrosine kinase 7 (PTK7)-positive cancer cells and subsequently cleaved via Fenton's reaction, resulting in rapid release kinetics, nuclear accumulation, and enhanced cytotoxicity of their cargo. In vivo experiments further confirmed that Sgc8-NFs-Fc has good tumor-targeting ability and could significantly improve the therapeutic efficacy of doxorubicin in a xenograft tumor model. On the basis of their tunable size and on-demand drug release kinetics upon H 2 O 2 stimulation, the Sgc8-NFs-Fc nanocarriers possess promising potential in drug delivery.

Despite the importance of naturally available wild pollination ecosystem services in enhancing sub-Saharan African smallholder farms' productivity, their values to actual farming systems remain unknown. We develop a nationally representative empirical assessment by integrating nationally representative plot level panel data with spatially and temporally matched land cover maps to identify the contribution of wild pollinators to crop revenue. Our estimation results reveal distinct and robust contributions by natural habitats of wild pollinators - forests - to plot-level crop revenue, where habitats in near proximity to plots contribute much more value than those farther away. When contrasting between pollinator-dependent and pollinator-independent crops, we find that the positive effects emerge only for pollinator-dependent crops, while pollinator-independent crops show no benefits. We conclude the empirical assessment by using our estimates to evaluate changes in crop revenue associated with the actual habitat reduction during 2008-2013. We find that this change in the natural habitats of wild pollinators has reduced crop revenue possibly by as much as 29% (mean) and 4% (median). To our knowledge, this is the first empirical assessment to use nationally representative smallholder farms to assess the value of naturally available wild pollination ecosystem services. Our results magnify the documented benefits of forest conservation, as this preserves pollinators' natural habitats, and by extension its inhabitants, who play an important role in boosting crop yields of nature dependent smallholder farms.

Developing a convenient method to discriminate among different types of DNA nucleotides within a target sequence of the human genome is extremely challenging. We herein report an artificial ferrocene-base (Fe-base) that was synthesized and incorporated into different loci of a DNA strand. The Fe-base replacement on a nucleobase can interact with DNA bases and efficiently discriminate among A, T, G, and C DNA bases of the complementary locus on the basis of interacting electrochemical properties. Furthermore, cyclic-voltammetry (CV) studies demonstrated the electrochemical stability of DNA strands incorporated with Fe-bases and the reversibility of the incorporation. Square-wave voltammetry (SWV) was performed to measure current changes between Fe-bases and bases of interest in the DNA duplex. The changes in the charge-transfer rates appeared to be correlated with the position of the Fe-base in the DNA strand, allowing rapid and efficient sensing of single-nucleobase changes in DNA and showing promise for the design of Fe-oligomer chip technology as a tool for DNA sequencing.

Lambda-cyhalothrin (λ-cyhalothrin) is the most commonly used pyrethroid insecticide for vegetable farming in Benin. This insecticide is misused and overused by farmers, and hence may pose health hazards to consumers. We monitored λ-cyhalothrin residues in lettuce and cabbage from farms at the market gates in Cotonou and Parakou using high performance liquid chromatography (HPLC) analysis techniques. These residues were also monitored on samples directly from farms (on-farm sampling) for 14 days post-treatment. Potential factors such as photolysis and hydrolysis involved in λ-cyhalothrin degradation were also screened. Results revealed that the level of λ-cyhalothrin residue concentrations in lettuce from Houeyiho decreased from 4.2 mg/kg on Day 1 to about 0.2 mg/kg on Day 7. On Day 9, analyzed lettuces were all λ-cyhalothrin free. In contrast, even 14 days after treatment of cabbage from Bawera (Parakou), we still recorded the presence of λ-cyhalothrin residues in analyzed samples. For samples from market gates, λ-cyhalothrin residues were found in lettuce from two markets out of the nine surveyed in Cotonou. Interestingly, none of these contaminated samples had residues above the maximum residue limit for lettuce (MRL = 0.5 mg/kg). Similarly, in Parakou, samples from all five surveyed vegetable markets were contaminated with λ-cyhalothrin residues at concentrations below the MRL for cabbage (MRL = 0.2 mg/kg). We conclude that λ-cyhalothrin residues in lettuce and cabbage from farms and markets in Parakou and Cotonou are within the MRL, and hence are relatively safe for consumption.

Background: The environmental pathogen, Mycobacterium ulcerans (MU) can infect both humans and animals and cause Buruli ulcer (BU) disease. However, its mode(s) of transmission from the colonized environment to human/animal hosts remain unclear. In Australia, MU can infect both wildlife and domestic mammals. Till date, BU-like lesions have only been reported in wildlife in Africa. This warrants a thorough assessment of possible MU in domestic animals in Africa. Here, we screened roaming domesticated animals that share the human microhabitat in two different BU endemic sites, Sedje-Denou in Benin and Akonolinga in Cameroon, for MU lesions., Methodology/principal Findings: We screened roaming mammals and birds across 3 endemic villages of Sedje-Denou in Southern Benin and 6 endemic villages of Akonolinga in Cameroon. After approval from relevant authorities, specimens (wound swabs and tissue fragments) were collected from animals with open or active lesion and systematically screened to detect the presence of MU though the diagnostic DNA targets IS2404, IS2606 and KR-B. Out of 397 animals surveyed in Akonolinga, 44 (11.08%) carried skin lesions and all were negative for MU DNA. For Sedje-Denou, only 25 (6.93%) out of 361 animals surveyed carried external skin lesions of which 2 (8%) were positive for MU DNA targets. These MU infected lesions were found in two different villages on a goat (abdominal part) and on a dog (nape area of the neck). Source-tracking of MU isolates within infected animal lesions was performed using VNTR genotyping and further confirmed with sequencing. One MU VNTR genotype (Z) was successfully typed from the goat lesion. The evolutionary history inferred from sequenced data revealed a clustering of animal MU isolates within isolates from human lesions., Conclusion/significance: This study describes the first report of two MU infected lesions in domestic animals in Africa. Their DNA sequence analyses show close relationship to isolates from human cases. It suggests that MU infection should be suspected in domestic hosts and these could play a role in transmission. The findings further support the hypothesis that MU is a ubiquitous environmental pathogen found in endemic areas, and probably involved in a multiple transmission pathway., Competing Interests: The authors have declared that no competing interests exist.

Background: Insecticides resistance in Anopheles mosquitoes limits Long-Lasting Insecticidal Nets (LLIN) used for malaria control in Africa, especially Benin. This study aimed to evaluate the bio-efficacy of current LLINs in an area where An. funestus s.l. and An. gambiae have developed multi-resistance to insecticides, and to assess in experimental huts the performance of a mixed combination of pyrethroids and piperonyl butoxide (PBO) treated nets on these resistant mosquitoes. Methods: The study was conducted at Kpomè, Southern Benin. The bio-efficacy of LLINs against An. funestus and An. gambiae was assessed using the World Health Organization (WHO) cone and tunnel tests. A released/recapture experiment following WHO procedures was conducted to compare the efficacy of conventional LLINs treated with pyrethroids only and LLINs with combinations of pyrethroids and PBO. Prior to huts trials, we confirmed the level of insecticide and PBO residues in tested nets using high performance liquid chromatography (HPLC). Results: Conventional LLINs (Type 2 and Type 4) have the lowest effect against local multi-resistant An. funestus s.s. and An. coluzzii populations from Kpomè. Conversely, when LLINs containing mixtures of pyrethroids and PBO (Type 1 and Type 3) were introduced in trial huts, we recorded a greater effect against the two mosquito populations (P < 0.0001). Tunnel test with An. funestus s.s. revealed mortalities of over 80% with this new generation of LLINs (Type 1 and Type 3),while conventional LLINs produced 65.53 ± 8.33% mortalities for Type 2 and 71.25 ±7.92% mortalities for Type 4. Similarly, mortalities ranging from 77 to 87% were recorded with the local populations of An. coluzzii . Conclusion: This study suggests the reduced efficacy of conventional LLINs (Pyrethroids alone) currently distributed in Benin communities where Anopheles populations have developed multi-insecticide resistance. The new generation nets (pyrethroids+PBO) proved to be more effective on multi-resistant populations of mosquitoes., Competing Interests: No competing interests were disclosed.

Background: To optimize the success of insecticide-based malaria control intervention, knowledge of the distribution of Anopheles gambiae species and insecticide resistance mechanisms is necessary. This paper reported an updated data on pyrethroids/DDT resistance in the An. gambiae s.l population from Togo.  Methods: From December 2013 to April 2015, females of indoor-resting An. gambiae s.l were captured in three locations belonging to three different ecological zones. Resistance to DDT, permethrin and deltamethrin was screened in F1 progeny of collected mosquitoes using WHO susceptibility tests. The identification of species of An. gambiae complex and the detection of kdr and ace.1 R allele were carried out using DNA-based molecular techniques. Results: An. gambiae from Kovié and Nangbéto were highly resistant to DDT and permethrin with mortalities rate ranging from 0.83% to 1.58% for DDT and zero to 8.54% for permethrin. Mosquitoes collected in Nangbéto displayed 81.53% mortality with deltamethrin. An. coluzzii and An. gambiae s.s were found in sympatry in Nangbéto and Mango . The allelic frequency of L1014F was high, ranging from 66 to 100% in both An. coluzzii and An. gambiae s.s . For the first time we detected the L1014S allele in both An. coluzzii and An. gambiae s.s. from Togo at the frequency ranging from 5% to 13% in all the sites. The kdr N1575Y was present at various frequencies in both species ranging from 10% to 45%. Both An. gambiae s.s. and An. coluzzii shared the ace1 R mutation in all investigated sites with allelic frequency ranging from 4% to 16%. Conclusion: These results showed that multiple mutations are involved in insecticides resistance in An. gambiae populations from Togo including the kdr L1014F, L1014S, and N1575Y and ace.1 R G119S mutations., Competing Interests: No competing interests were disclosed.

Background: Buruli ulcer (BU) continues to be a serious public health threat in wet tropical regions and the mode of transmission of its etiological agent, Mycobacterium ulcerans ( MU ), remains poorly understood. In this study, mosquito species collected in endemic villages in Benin were screened for the presence of MU . In addition, the ability of mosquitoes larvae to pick up MU from their environment and remain colonized through the larval developmental stages to the adult stage was investigated., Methods: 7,218 adults and larvae mosquitoes were sampled from endemic and nonendemic villages and screened for MU DNA targets ( IS2404 , IS2606 , and KR-B) using qPCR. Results. MU was not detected in any of the field collected samples. Additional studies of artificially infected larvae of Anopheles kisumu with MU strains revealed that mosquitoes larvae are able to ingest and host MU during L1, L2, L3, and L4 developmental stages. However, we noticed an absence of these bacteria at both pupae and adult stages, certainly revealing the low ability of infected or colonized mosquitoes to vertically transmit MU to their offspring., Conclusion: The overall findings highlight the low implication of mosquitoes as biological vectors in the transmission cycle of MU from the risk environments to humans.

Background: Several studies have reported the implication of HLA-DR/DQ loci in the susceptibility to type 1 diabetes (T1D). Since no such study has yet been performed in Benin, this pilot one aimed at assessing HLA class II allele, haplotype, and genotype associations with T1D., Material and Methods: Class II HLA genotyping was performed in 51 patients with T1D and 51 healthy unrelated controls by means of the PCR-SSP method. The diagnosis of T1D was set up according to American Diabetes Association criteria. Odds ratio (OR) and its 95% confidence interval (95% CI) were calculated to assess the associations between T1D and HLA alleles, haplotypes, and genotypes., Results: Participants were aged 1-24 years. T1D was significantly associated with DR3, DQA1∗05:01, DQB1∗02:01, and DR3-DR4. No significant associations were observed with DR4, DQB1∗03:02, and DQB1∗06:02., Conclusion: Certain HLA class II alleles, haplotypes, and genotypes were related to T1D and may be used as genetic susceptibility markers to T1D in Benin.

Background: Knowledge on the spread and distribution of insecticide resistance in major malaria vectors such as Anopheles funestus is key to implement successful resistance management strategies across Africa. Here, by assessing the susceptibility status of an inland population of An. funestus Giles (Kpome) and investigating molecular basis of resistance, we show that multiple resistance and consistent plasmodium infection rate are present in Anopheles funestus populations from Kpome., Methods: The insecticide susceptibility level of collected Anopheles funestus was assessed. Synergist (PBO) was used to screen resistance mechanisms. The TaqMan technique was used for genotyping of insecticide resistant alleles and detecting plasmodium infection levels. The nested PCR was used to further assess the plasmodium infection rate., Results: The TaqMan analysis of plasmodial infections revealed an infection rate (18.2 %) of An. funestus in this locality. The WHO bioassays revealed a multiple phenotypic resistance profile for An. funestus in Kpome. This population is highly resistant to pyrethroids (permethrin and deltamethrin), organochlorines (DDT), and carbamates (bendiocarb). A reduced susceptibility was observed with dieldrin. Mortalities did not vary after pre-exposure to PBO for DDT indicating that cytochrome P450s play little role in DDT resistance in Kpome. In contrast, we noticed, a significant increase in mortalities when PBO was combined to permethrin suggesting the direct involvement of P450s in pyrethroid resistance. A high frequency of the L119F-GSTe2 DDT resistance marker was observed in the wild DDT resistant population (9 %RS and 91 %RR) whereas the A296S mutation was detected at a low frequency (1 %RS and 99 %SS)., Conclusion: The presence of multiple resistance in An. funestus populations in the inland locality of Kpome is established in this study as recently documented in the costal locality of Pahou. Data from both localities suggest that resistance could be widespread in Benin and this highlights the need for further studies to assess the geographical distribution of insecticide resistance across Benin and neighboring countries as well as a more comprehensive analysis of the resistance mechanisms involved.