Evaluation of the Newborn Screening Pilot for Sickle Cell Disease in Suriname Using the Non-Adoption, Abandonment, Scale-Up, Spread, and Sustainability (NASSS) Framework.

The early detection of sickle cell disease (SCD) is vital to reduce mortality among affected children. Suriname currently lacks a newborn screening programme (NSP) for SCD. We performed a pilot programme to evaluate the scalability of such an initiative. Dried blood spots were collected from five birth centres and subjected to electrophoresis analysis. The programme scalability was evaluated using the non-adoption, abandonment, scale-up, spread, and sustainability framework. Challenges across six domains (illness, technology, value proposition, adopter system, organisation, and societal system), were categorised hierarchically as simple 😊, complicated 😐, or complex 😢. It has been proven that implementing programmes with mainly complicated challenges is difficult and those in mainly complex areas may be unachievable. SCD was detected in 33 of 5185 (0.64%) successfully screened newborns. Most of the domains were classified as simple or complicated. Disease detection and technology suitability for screening in Suriname were confirmed, with favourable parental acceptance. Only minor routine adjustment was required from the medical staff for programme implementation. Complex challenges included a reliance on external suppliers for technical maintenance, ensuring timely access to specialised paediatric care for affected newborns, and securing sustainable financial funding. Scaling up is challenging but feasible, particularly with a targeted focus on identified complex challenges.

Characterization of Urinary Pesticide Metabolite Concentrations of Pregnant Women in Suriname.

Prenatal exposure to pesticides and the association with adverse health outcomes have been examined in several studies. However, the characterization of pesticide exposure among Surinamese women during pregnancy has not been assessed. As part of the Caribbean Consortium of Research in Environmental and Occupational Health research program, 214 urine samples were collected from pregnant women living in three regions in Suriname with different agricultural practices: capital Paramaribo, the rice producing district Nickerie, and the tropical rainforest, the Interior. We used isotope dilution tandem mass spectrometry to quantify urinary concentrations of biomarkers of three pesticide classes, including phenoxy acid herbicides and organophosphate and pyrethroid insecticides, all of which are commonly used in agricultural and residential settings in Suriname. We observed that participants residing in Nickerie had the highest urinary metabolite concentrations of 2,4-dichlorophenoxyacetic acid and pyrethroids compared to those from Paramaribo or the Interior. Paramaribo had the highest concentrations of organophosphate metabolites, specifically dialkyl phosphate metabolites. Para-nitrophenol was detected in samples from Paramaribo and the Interior. Samples from Nickerie had higher median urinary pesticide concentrations of 2,4-dichlorophenoxyacetic acid (1.06 µg/L), and the following metabolites, 3,5,6-trichloro-2-pyridinol (1.26 µg/L), 2-isopropyl-4-methyl-6-hydroxypyrimidine (0.60 µg/L), and 3-phenoxybenzoic acid (1.34 µg/L), possibly due to residential use and heavy rice production.

Caribbean Consortium for Research in Environmental and Occupational Health (CCREOH) Cohort Study: influences of complex environmental exposures on maternal and child health in Suriname.

PURPOSE: The Caribbean Consortium for Research in Environmental and Occupational Health prospective environmental epidemiologic cohort study addresses the impact of chemical and non-chemical environmental exposures on mother/child dyads in Suriname. The study determines associations between levels of environmental elements and toxicants in pregnant women, and birth outcomes and neurodevelopment in their children. PARTICIPANTS: Pregnant women (N=1143) were enrolled from December 2016 to July 2019 from three regions of Suriname: Paramaribo (N=738), Nickerie (N=204) and the tropical rainforest interior (N=201). Infants (N=992) were enrolled at birth. Follow-up will take place until children are 48 months old. FINDINGS TO DATE: Biospecimens and questionnaire data on physiological and psychosocial health in pregnant women have been analysed. 39.1% had hair mercury (Hg) levels exceeding values considered safe by international standards. Median hair Hg concentrations in women from Paramaribo (N=522) were 0.64 µg/g hair (IQRs 0.36-1.09; range 0.00-7.12), from Nickerie (N=176) 0.73 µg/g (IQR 0.45-1.05; range 0.00-5.79) and the interior (N=178) 3.48 µg/g (IQR 1.92-7.39; range 0.38-18.20). 96.1% of women ate fish, respective consumption of the three most consumed carnivorous species, Hoplias aimara, Serrasalmus rhombeus and Cichla ocellaris, known to have high Hg levels, was 44.4%, 19.3% and 26.3%, respectively, and was greater among the interior subcohort. 89% frequently consumed the vegetable tannia, samples of which showed presence of worldwide banned pesticides. 24.9% of pregnant women had Edinburgh Depression Scale scores indicative of probable depression. FUTURE PLANS: Fish consumption advisories are in development, especially relevant to interior women for whom fish consumption is likely to be the primary source of Hg exposure. Effects of potentially beneficial neuroprotective factors in fish that may counter neurotoxic effects of Hg are being examined. A pesticide literacy assessment in pregnant women is in progress. Neurodevelopmental assessments and telomere length measurements of the children to evaluate long-term effects of prenatal exposures to toxicant mixtures are ongoing.

Chronic Neurology in COVID-19 Era: Clinical Considerations and Recommendations From the REPROGRAM Consortium.

With the rapid pace and scale of the emerging coronavirus 2019 (COVID-19) pandemic, a growing body of evidence has shown a strong association of COVID-19 with pre- and post- neurological complications. This has necessitated the need to incorporate targeted neurological care for this subgroup of patients which warrants further reorganization of services, healthcare workforce, and ongoing management of chronic neurological cases. The social distancing and the shutdown imposed by several nations in the midst of COVID-19 have severely impacted the ongoing care, access and support of patients with chronic neurological conditions such as Multiple Sclerosis, Epilepsy, Neuromuscular Disorders, Migraine, Dementia, and Parkinson disease. There is a pressing need for governing bodies including national and international professional associations, health ministries and health institutions to harmonize policies, guidelines, and recommendations relating to the management of chronic neurological conditions. These harmonized guidelines should ensure patient continuity across the spectrum of hospital and community care including the well-being, safety, and mental health of the patients, their care partners and the health professionals involved. This article provides an in-depth analysis of the impact of COVID-19 on chronic neurological conditions and specific recommendations to minimize the potential harm to those at high risk.

Zika virus outbreak in Suriname, a report based on laboratory surveillance data.

INTRODUCTION: Since the identification of ZIKV in Brazil in May 2015, the virus has spread extensively throughout the Americas. Cases of ZIKV infection have been reported in Suriname since October 2, 2015. METHODS: A laboratory-based surveillance system was quickly implemented according to previous experience with the emergence of chikungunya. General practitioners and public health centers located in different districts of Suriname were asked to send blood samples from suspicious cases to Academic Hospital for molecular diagnosis of Zika virus infection. We investigated Zika-related laboratory data collected during surveillance and response activities to provide the first outbreak report in Suriname in terms of time, location and person. RESULTS: A total of 791 molecularly confirmed cases were reported during a 48-week interval from October 2015 to August 2016. The majority of ZIKV-positive cases involved women between 20 and 39 years of age, reflecting concern about Zika infection during pregnancy. The outbreak peaked in mid-January and gradually spread from the district of Paramaribo to western coastal areas. DISCUSSION: This report provides a simple and comprehensive description of the outbreak in Suriname and demonstrates the utility of laboratory data to highlight the spatiotemporal dynamics of the outbreak in that country.

The influence of miniscrew insertion torque.

Objective: The aim of this in vitro study was to evaluate the progressive development of surface microdamage produced following the insertion of orthodontic miniscrews (OMs) into 1.5 mm thick porcine tibia bone using maximum insertion torque values of 12 Ncm, 18 Ncm, and 24 Ncm. Methods: Aarhus OMs (diameter 1.5 mm; length 6 mm) were inserted into 1.5 mm porcine bone using a torque limiting hand screwdriver set at 12 Ncm, 18 Ncm, and 24 Ncm. A custom rig equipped with a compression load cell was used to record the compression force exerted during manual insertion. A sequential staining technique was used to identify microdamage viewed under laser confocal microscopy. Virtual slices were created and stitched together to form a compressed two-dimensional composition of the microdamage. Histomorphometric parameters, including total damage area, diffuse damage area, maximum crack length, maximum damage radius, and maximum diffuse damage radius, were measured. Kruskal-Wallis Tests and Wilcoxon Rank-Sum Tests were used to analyse the generated data. Results: All OMs inserted using 12 Ncm failed to insert completely, while partial insertion was observed for two OMs inserted at 18 Ncm. Complete insertion was achieved for all OMs inserted at 24 Ncm. Histomorphometrically, OMs inserted using 24 Ncm produced a significantly larger diffuse damage area (P < 0.05; P < 0.05) and maximum diffuse damage radius (P < 0.05; P < 0.05), for both the entry and exit surfaces, respectively, compared with the 12 Ncm and 18 Ncm groups. Conclusions: Insertion torque can influence the degree of OM insertion and, subsequently, the amount of microdamage formed following insertion into 1.5 mm thick porcine tibia bone. An increase in insertion torque corresponds with greater insertion depth and larger amounts of microdamage.

Severity of acute Zika virus infection: A prospective emergency room surveillance study during the 2015-2016 outbreak in Suriname.

Acute Zika virus (ZIKV) infection is usually mild and self-limiting. Earlier, we reported three cases of fatal acute ZIKV infection in patients without typical signs of ZIKV, but rather with criteria of systemic inflammation response syndrome (SIRS). To follow up these observations, we prospectively included patients at the emergency room with temperature instability and suspected to have acute ZIKV infection, SIRS, or both. A total of 102 patients were included of whom N = 21 (21%) were suspected of acute ZIKV infection, N = 56 (55%) of acute ZIKV infection with SIRS criteria, and N = 25 (24%) of SIRS alone. ZIKV-PCR was positive in N = 21 (20%) patients. Eight (38%) ZIKV-positive patients needed admission to the hospital of whom four (50%) presented with SIRS alone. One ZIKV-positive patient had vascular co-morbidity and died following shock and severe coagulopathy. We confirm the hypothesis that acute ZIKV infection can present atypical and severely with systemic inflammation and have lethal course particularly amongst patients with significant prior disease.

Severity of acute Zika virus infection: A prospective emergency room surveillance study during the 2015­2016 outbreak in Suriname

Acute Zika virus (ZIKV) infection is usually mild and self-limiting. Earlier, we reported three cases of fatal acute ZIKV infection in patients without typical signs of ZIKV, but rather with criteria of systemic inflammation response syndrome (SIRS). To follow up these observations, we prospectively included patients at the emergency room with temperature instability and suspected to have acute ZIKV infection, SIRS, or both. A total of 102 patients were included of whom N =21 (21%) were suspected of acute ZIKV infection, N =56 (55%) of acute ZIKV infection with SIRS criteria, and N =25 (24%) of SIRS alone. ZIKV-PCR was positive in N =21 (20%) patients. Eight (38%) ZIKV-positive patients needed admission to the hospital of whom four (50%) presented with SIRS alone. One ZIKV-positive patient had vascular co-morbidity and died following shock and severe coagulopathy. We confirm the hypothesis that acute ZIKV infection can present atypical and severely with systemic inflammation and have lethal course particularly amongst patients with significant prior disease...(AU)

Influence of cortical bone thickness on miniscrew microcrack formation.

INTRODUCTION: The aim of this in-vitro study was to investigate the influence of cortical bone thickness on the amount of surface microdamage produced after insertion of orthodontic miniscrews (OM) in porcine tibia bone. METHODS: Aarhus OMs (Medicon, Tuttlingen, Germany; diameter, 1.5 mm; length, 6 mm) were inserted into 1.0 mm (group A; n = 10), 1.5 mm (group B; n = 10), and 2.0 mm (group C; n = 10) of porcine cortical bone using a torque-limiting hand screwdriver set at 18 Ncm. A sequential staining technique was used to identify microdamage under laser confocal microscopy. Virtual slices were stitched together using ImageJ software (National Institutes of Health, Bethesda, Md) to form a compressed 2-dimensional composition of the microdamage. The ImageJ software was used to quantify the total damage area, diffuse damage area, maximum crack length, maximum damage radius, and maximum diffuse damage radius. Kruskal-Wallis tests and Wilcoxon rank sum tests were used to analyze the data. RESULTS: All OMs in group A (1.0 mm) were inserted completely; however, 2 OMs from group B (1.5 mm) and all OMs in group C (2.0 mm) failed to insert completely. The entry surface of group C (2.0 mm) exhibited significantly higher amounts of total damage, diffuse damage area, maximum crack length, and maximum crack damage radius compared with groups A (1.0 mm) and B (1.5 mm). The maximum crack length observed on the entry and exit surfaces ranged from 1.03 to 3.06 mm. CONCLUSIONS: In this study, we demonstrated a higher level of microdamage after the insertion of OMs into 2.0-mm thick cortical bone compared with 1.0-mm thick cortical bone. Therefore, clinicians need to consider the thickness of the cortical bone at the insertion site, because mechanisms to reduce cortical bone thickness would likely reduce the amount of microdamage formed. A safety zone of 3.5 mm from the OM is also recommended for OMs inserted into 1.0- and 1.5-mm cortical bone thicknesses to minimize any detrimental effects after targeted remodeling.

mTORC1 Plays an Important Role in Skeletal Development by Controlling Preosteoblast Differentiation.

The mammalian target of rapamycin complex 1 (mTORC1) is activated by extracellular factors that control bone accrual. However, the direct role of this complex in osteoblast biology remains to be determined. To investigate this question, we disrupted mTORC1 function in preosteoblasts by targeted deletion of Raptor (Rptor) in Osterix-expressing cells. Deletion of Rptor resulted in reduced limb length that was associated with smaller epiphyseal growth plates in the postnatal skeleton. Rptor deletion caused a marked reduction in pre- and postnatal bone accrual, which was evident in skeletal elements derived from both intramembranous and endochondrial ossification. The decrease in bone accrual, as well as the associated increase in skeletal fragility, was due to a reduction in osteoblast function. In vitro, osteoblasts derived from knockout mice display a reduced osteogenic potential, and an assessment of bone-developmental markers in Rptor knockout osteoblasts revealed a transcriptional profile consistent with an immature osteoblast phenotype suggesting that osteoblast differentiation was stalled early in osteogenesis. Metabolic labeling and an assessment of cell size of Rptor knockout osteoblasts revealed a significant decrease in protein synthesis, a major driver of cell growth. These findings demonstrate that mTORC1 plays an important role in skeletal development by regulating mRNA translation during preosteoblast differentiation.

EZH2 deletion in early mesenchyme compromises postnatal bone microarchitecture and structural integrity and accelerates remodeling.

In this study, we examined the functional importance of EZH2 during skeletal development and homeostasis using the conditional deletion of Ezh2 (Ezh2fl/fl ) in early mesenchyme with the use of a Prrx-1-cre driver mouse (Ezh2+/+). Heterozygous (Ezh2+/-) newborn and 4-wk-old mice exhibited increased skeletal size, growth plate size, and weight when compared to the wild-type control (Ezh2+/+), whereas homozygous deletion of Ezh2 (Ezh2-/-) resulted in skeletal deformities and reduced skeletal size, growth plate size, and weight in newborn and 4-wk-old mice. Ezh2-/- mice exhibited enhanced trabecular patterning. Osteogenic cortical and trabecular bone formation was enhanced in Ezh2+/- and Ezh2-/- animals. Ezh2+/- and Ezh2-/- mice displayed thinner cortical bone and decreased mechanical strength compared to the wild-type control. Differences in cortical bone thickness were attributed to an increased number of osteoclasts, corresponding with elevated levels of the bone turnover markers cross-linked C-telopeptide-1 and tartrate-resistant acid phosphatase, detected within serum. Moreover, Ezh2+/- mice displayed increased osteoclastogenic potential coinciding with an upregulation of Rankl and M-csf expression by mesenchymal stem cells (MSCs). MSCs isolated from Ezh2+/- mice also exhibited increased trilineage potential compared with wild-type bone marrow stromal/stem cells (BMSCs). Gene expression studies confirmed the upregulation of known Ezh2 target genes in Ezh2-/- bone tissue, many of which are involved in Wnt/BMP signaling as promoters of osteogenesis and inhibitors of adipogenesis. In summary, EZH2 appears to be an important orchestrator of skeletal development, postnatal bone remodelling and BMSC fate determination in vitro and in vivo-Hemming, S., Cakouros, D., Codrington, J., Vandyke, K., Arthur, A., Zannettino, A., Gronthos, S. EZH2 deletion in early mesenchyme compromises postnatal bone microarchitecture and structural integrity and accelerates remodeling.

Three atypical lethal cases associated with acute Zika virus infection in Suriname.

Acute Zika virus infection usually presents with a self-limiting triad of fever, rash and arthritis. There is limited information on severe or lethal cases. We report three cases of lethal acute Zika infection, confirmed with polymerase chain reaction, in adult patients with some co-morbidities. The patients showed rapid clinical deterioration with hemorrhagic and septic shock, and exaggerated acute and innate inflammatory responses with pronounced coagulopathy, and died soon after admission to the hospital. It remains unclear whether the fatal outcomes were due to acute Zika virus infection alone or to the combination with exacerbated underlying prior disease or co-infection. Nonetheless, the severity of these cases implies that increased awareness for atypical presentations of Zika virus infection, and careful clinical assessment of patients with symptoms of Zika, is warranted during current and future outbreaks.

Prevalence, determinants and genetic diversity of hepatitis C virus in the multi-ethnic population living in Suriname.

Little is known about the epidemiology of HCV in Suriname, a former Dutch colony in South America. To study the prevalence, determinants and genetic diversity of HCV, a one-month survey was conducted at the only Emergency Department in the capital Paramaribo. Participants (≥18 years) completed an interviewer-led standardized HCV risk-factor questionnaire, were tested for HCV-antibodies, and if positive also for HCV RNA. The overall HCV prevalence was 1.0% (22/2128 participants; 95%CI 0.7-1.5). Male sex (OR=4.11; 95%CI 1.30-13.01), older age (OR=1.06 per year increase; 95%CI 1.04-1.09), Javanese ethnicity (OR=7.84; 95%CI 3.25-18.89) and cosmetic tattooing (OR=31.7; 95%CI 3.25-323.87) were independently associated with HCV-infection. Phylogenetic analysis revealed six distinct HCV subtypes, all HCV-genotype 2 (HCV-2): subtype 2f (also circulating in Indonesia) plus five yet unassigned HCV-2 subtypes exclusively linked to Suriname.

Causes of Flexor Tendon Repair Failures in Two Common Repair Techniques: A Cadaver Study.

BACKGROUND: Flexor tendon repair failures have primarily been attributed to either core suture rupture or core suture pull out. Recent studies have suggested that knot unravelling may also cause failure of a tendon repair. The aim of this study was to investigate the causes of core suture failure in two types of common flexor tendon repairs. METHODS: Twenty four cadaver tendons were divided into three groups of eight. Each group tested a specific flexor tendon repair. The repairs tested included an Adelaide repair using 4/0 Ethibond (Ethicon), an Adelaide repair using 4/0 Fiberwire (Arthrex) and the Tsai repair with 4/0 Fiberloop (Arthrex). The repaired tendons were pull-tested to failure. The mechanism of failure, maximum tensile strength and 2 mm gap force were recorded. RESULTS: The predominant mode of failure was by the knot unravelling. This occurred in 50-88% of the tendon repairs. The sequence of failure was initiated with gapping at the repair site followed by failure of the epitendinous suture. Next the core suture knot unravels. Once the knot unravels, the suture thread slips out of the tendon resulting in the repair failure. Failures due to knot slippage occurred at a lower maximum tensile strength in Ethibond and Fiberloop sutures than failure due to core rupture or pull out. However, given the small number of tendons tested, this result was not significant. CONCLUSIONS: This study has clearly demonstrated one of the main causes of flexor tendon repair failure in two common repair techniques is knot unravelling.

Loss of ephrinB1 in osteogenic progenitor cells impedes endochondral ossification and compromises bone strength integrity during skeletal development.

The EphB receptor tyrosine kinase family and their ephrinB ligands have been implicated as mediators of skeletal development and bone homeostasis in humans, where mutations in ephrinB1 contribute to frontonasal dysplasia and coronal craniosynostosis. In mouse models, ephrinB1 has been shown to be a critical factor mediating osteoblast function. The present study examined the functional importance of ephrinB1 during endochondral ossification using the Cre recombination system with targeted deletion of ephrinB1 (EfnB1fl/fl) in osteogenic progenitor cells, under the control of the osterix (Osx:Cre) promoter. The Osx:EfnB1-/- mice displayed aberrant bone growth during embryonic and postnatal skeletal development up to 4weeks of age, when compared to the Osx:Cre controls. Furthermore, compared to the Osx:Cre control mice, the Osx:EfnB1-/- mice exhibited significantly weaker and less rigid bones, with a reduction in trabecular/ cortical bone formation, reduced trabecular architecture and a reduction in the size of the growth plates at the distal end of the femora from newborn through to 4weeks of age. The aberrant bone formation correlated with increased numbers of tartrate resistant acid phosphatase positive osteoclasts and decreased numbers of bone lining osteoblasts in 4week old Osx:EfnB1-/- mice, compared to Osx:Cre control mice. Taken together, these observations demonstrate the importance of ephrinB1 signalling between cells of the skeleton required for endochondral ossification.

Three atypical lethal cases associated with acute Zika virus infection in Suriname

Acute Zika virus infection usually presents with a self-limiting triad of fever, rash and arthritis. There is limited information on severe or lethal cases. We report three cases of lethal acute Zika infection, confirmed with polymerase chain reaction, in adult patients with some co-morbidities. The patients showed rapid clinical deterioration with hemorrhagic and septic shock, and exaggerated acute and innate inflammatory responses with pronounced coagulopathy, and died soon after admission to the hospital. It remains unclear whether the fatal outcomes were due to acute Zika virus infection alone or to the combination with exacerbated underlying prior disease or co-infection. Nonetheless, the severity of these cases implies that increased awareness for atypical presentations of Zika virus infection, and careful clinical assessment of patients with symptoms of Zika, is warranted during current and future outbreaks...(AU)

A Case of Lagochilascariasis in Suriname with the Involvement of the ENT System and the Skull Base.

We describe a case of human lagochilascariasis, with skull-base involvement and a chronic and relapsing course after treatment. This rare parasitic infection is usually manifested in the head and neck area, characterized by progressive granulomatous inflammation and the formation of abscesses. Transmission to humans most likely occurs by the consumption of undercooked meat of wild rodents. On the basis of literature studies, we propose the most likely life cycle of the parasite that involves wild feline and rodent species, with humans as accidental hosts. Even in endemic areas, it is very difficult to recognize the disease at an early stage. Progression will eventually lead to involvement of the (central) nervous system, as described in our case. Treatment is often difficult and involves resection and prolonged treatment with anthelmintic drugs. Recurrences are not uncommon and at present, long-term oral administration of ivermectin seems to be the most effective treatment.