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The use of saliva as a diagnostic biofluid has been increasing in recent years, thanks to the identification and validation of new biomarkers and improvements in test accuracy, sensitivity, and precision that enable the development of new noninvasive and cost-effective devices. However, the lack of standardized methods for sample collection, treatment, and storage contribute to the overall variability and lack of reproducibility across analytical evaluations. Furthermore, the instability of salivary biomarkers after sample collection hinders their translation into commercially available technologies for noninvasive monitoring of saliva in home settings. The present review aims to highlight the status of research on the challenges of collecting and using diagnostic salivary samples, emphasizing the methodologies used to preserve relevant proteins, hormones, genomic, and transcriptomic biomarkers during sample handling and analysis.

The purpose of this study was to examine the clinical indication for laparotomy, the intra-operative findings and the 30 days post-operative outcome of laparotomy in Gulu university teaching hospitals.

The tumour microenvironment (TME) strongly influences tumorigenesis and metastasis. Two of the most characterized properties of the TME are acidosis and hypoxia, both of which are considered hallmarks of tumours as well as critical factors in response to anticancer treatments. Currently, various imaging approaches exist to measure acidosis and hypoxia in the TME, including magnetic resonance imaging (MRI), positron emission tomography and optical imaging. In this review, we will focus on the latest fluorescent-based methods for optical sensing of cell metabolism and MRI as diagnostic imaging tools applied both in vitro and in vivo. The primary emphasis will be on describing the current and future uses of systems that can measure intra- and extra-cellular pH and oxygen changes at high spatial and temporal resolution. In addition, the suitability of these approaches for mapping tumour heterogeneity, and assessing response or failure to therapeutics will also be covered., Comment: 36 pages, 13 figures

Introduction: Many HIV-positive individuals in Africa have advanced disease when initiating antiretroviral therapy (ART) so have high risks of opportunistic infections and death. The REALITY trial found that an enhanced-prophylaxis package including fluconazole reduced mortality by 27% in individuals starting ART with CD4

Embolization is a catheter-based minimally invasive procedure that deliberately occludes diseased blood vessels for treatment purposes. We report a novel silk based embolic material (SEM) that was developed and optimized to provide tandem integration of both embolization and the delivery of therapeutics. Natural silk was processed into fibroin proteins of varying lengths and combined with charged nanoclay particles to allow visibility and injectability using clinical catheters as small as 600 microns in diameter at lengths >100 cm. SEMs loaded with fluorochrome labeled bovine albumin and Nivolumab, which is among the most used immunotherapy drugs world-wide, demonstrated a sustained release profile in vitro over 28 days. In a porcine renal survival model, SEMs with labeled albumin and Nivolumab successfully embolized porcine arteries without recanalization and led to the delivery of both albumin and Nivolumab into the interstitial space of the renal cortex. Mechanistically, we show that tissue delivery is most optimal when the internal elastic membrane of the embolized artery is disrupted. SEM is a potential next-generation multifunctional embolic agent that can achieve embolization and deliver a wide range of therapeutics to treat vascular diseases including tumors. This article is protected by copyright. All rights reserved.

Background Viral load (VL) testing is key in monitoring adherence to antiretroviral therapy (ART) and documenting HIV treatment response. As per HIV treatment guidelines in Uganda, the first VL test is recommended 6 months after initiation of ART. Undetectable VL (uVL) at ART initiation may be helpful in detecting elite controllers in the absence of previous ART use. We investigated viral suppression at ART initiation among a cohort of HIV-positive pregnant women enrolled in the Friends for Life Circles (FLC) for Option B+ randomized controlled trial (RCT). Methods Pregnant women ≥ 18 years of age testing positive for HIV at their first antenatal care visit and starting on ART Option B+ as per the National PMTCT Program guidelines were enrolled into the FLC for Option B+ RCT in urban Kampala and rural Mityana districts of Uganda. Each participant had whole blood samples collected at enrolment to assess baseline VL. Plasma HIV-1 RNA was quantified using COBAS Ampliprep /COBAS Taqman. Baseline VL below 400 RNA copies/ml was considered as viral suppression while baseline VL below 20 RNA copies/ml was considered uVL. Results The mean duration from the date of ART initiation to time of sample collection for baseline VL assessment was 4.4 days (SD 3.6). Of the 532 HIV-positive pregnant women enrolled in the FLC for Option B+ study and newly starting Option B+ without a self-reported history of prior ART use, 29 (5.5%) had uVL and 113 (21.4%) had suppressed VL at baseline. There was no association between participants’ age, gravidity, marital status, mean monthly income, educational level, disclosure of HIV status to partner, and uVL or viral suppression at baseline. However, non-disclosure of HIV status to any other person was associated with decreased odds of viral suppression at baseline (OR 0.640; 0.416–0.982). Conclusion Twenty-one percent of HIV-positive Ugandan pregnant women initiating ART (Option B+) showed virological suppression at baseline and were presumed to be “elite controllers” or to have misreported being ART-naive. Further studies are needed to better understand the biologic mechanisms of elite controllers among pregnant women as well as to differentiate elite controllers from concealed ART use. Trial Registration The trial was registered as NCT02515370 (04/08/2015) on Clinicaltrials.gov.

BackgroundCOVID-19 impacted global maternal, neonatal and child health outcomes. We hypothesised that the early, strict lockdown which restricted individuals movements in Uganda limited access to services. MethodsAn observational study, using routinely collected data from Electronic Medical Records was carried out, in Kawempe district, Kampala. An interrupted time series analysis assessed the impact on maternal, neonatal, child, sexual and reproductive health services from July 2019 to December 2020. Descriptive statistics summarised the main outcomes before (July 2019 - March 2020), during (April 2020 - June 2020) and after the national lockdown (July 2020 - December 2020). ResultsBetween 1st July 2019 and 31st December 2020 there were 14,401 antenatal clinic attendances, 33,499 deliveries, 111,658 childhood service attendances and 57,174 for sexual health. All antenatal and vaccination services ceased in lockdown for four weeks. During the three-month lockdown, the number of antenatal attendances significantly decreased, and remain below pre-COVID levels (370 fewer/month). Attendances for prevention of mother-to-child transmission of HIV dropped then stabilised. Increases during lockdown and immediately postlockdown included the number of women treated for high blood pressure, eclampsia and pre-eclampsia (218 more/month), adverse pregnancy outcomes (stillbirths, low-birth-weight and premature infant births), the rate of neonatal unit admissions, neonatal deaths and abortions. Maternal mortality remained stable. Immunisation clinic attendance declined whilst neonatal death rate rose (from 39-49/1000 livebirths). The number of children treated for pneumonia, diarrhoea and malaria decreased during lockdown. ConclusionThe Ugandan response to COVID-19 negatively impacted maternal, child and neonatal health, with an increase seen in pregnancy complications, and fetal and infant outcomes, likely due to delayed care-seeking behaviour. Decreased vaccination clinic attendance leaves a cohort of infants unprotected, affecting all vaccine-preventable diseases. Future pandemic responses must consider impacts of movement restrictions and access to preventative services to protect maternal and child health. O_TEXTBOXKEY QUESTIONS What is already known?O_LIThe response to COVID-19 has been shown to have indirectly impacted on maternal, child, neonatal, sexual, and reproductive health. C_LIO_LIThis is largely related to access to services and fear of contracting COVID-19 in outpatient departments. C_LIO_LIThere has been very little data published on the health impacts of the COVID-19 response in Uganda. C_LI What are the new findings?O_LIAntenatal attendances decreased dramatically in April, followed by increased numbers low-birthweight infants and neonatal deaths. C_LIO_LINewborn immunisations against polio, tetanus, diphtheria, hepatitis B, haemophilus influenzae, rotavirus and pneumococcus decreased significantly. C_LIO_LISexual, and reproductive health services were reduced in number. C_LI What do the new findings imply?O_LIAlthough Uganda has been less affected directly by COVID-19 infections in the first wave, the indirect impacts are far-reaching and will have future influences on population health. C_LIO_LIThere is a degree of resilience within the healthcare service, but many services were adversely affected by the lockdown leading to poorer pregnancy and neonatal outcomes. C_LIO_LIAntenatal and vaccination services are of particular importance in ensuring the safety of mother and child and must be prioritised in the responses to future pandemics. C_LI C_TEXTBOX

Background HIV status awareness is critical for HIV prevention and care but HIV testing rates remain low in Uganda, especially among men. One suggested approach to increase access and utilisation of HIV testing services is HIV self-testing. We explored perceptions of pregnant and lactating women and their male partners who attended antenatal care, and health care providers in a government hospital in Kampala, Uganda, about HIV self-testing for initial or repeat testing for women and their partners during pregnancy and postpartum We draw implications for scaling-up this new testing approach in Uganda. Methods This was a qualitative study conducted at Mulago National Referral Hospital, Kampala, Uganda, between April and December 2017. We conducted in-depth interviews with five pregnant or lactating women and their five male partners; five focus group discussions (two with women, two with health workers and one with male partners of women attending antenatal care) and five key informant interviews with health workers providing prevention of mother-to-child HIV transmission (PMTCT) services. Data were analysed using content thematic approach. Results There was limited awareness about HIV self-testing especially among pregnant or lactating women and their male partners. Study participants mentioned that HIV self-testing would enable people to know their HIV status faster, they thought the approach would be cost- and time-saving compared to health facility-based HIV testing, improve confidentiality and reduce stigma for those who test HIV positive. They expressed however, a general fear that HIV self-testing would lead to harm to self and others in case one tested HIV positive, including suicide, violence among couples, intentional transmission of HIV, and limited linkage to care due to lack of counselling. The likely misinterpretation of HIV test results especially among those with no or limited education, and possible coercion exerted by male partners on their wives were other potential concerns raised about the use of HIV self-testing. Conclusions There was limited knowledge about HIV self-testing among pregnant and lactating women, their partners and health workers. While the self-testing modality was perceived to be critical for helping people, especially those in casual and distant relationships, to know their HIV status and that of their partners, most study participants believed that HIV self-testing could potentially result in a multitude of negative outcomes in the absence of pre- and post-test counselling. Successful scale-up and integration of self-testing in HIV programs requires community education, provision of information materials and making self-test kits accessible and affordable, especially in rural areas.

Electrospinning is historically related to tissue engineering due to its ability to produce nano-/microscale fibrous materials with mechanical and functional properties that are extremely similar to those of the extracellular matrix of living tissues. The general interest in electrospun fibrous matrices has recently expanded to cancer research both as scaffolds for in vitro cancer modelling and as patches for in vivo therapeutic delivery. In this review, we examine electrospinning by providing a brief description of the process and overview of most materials used in this process, discussing the effect of changing the process parameters on fiber conformations and assemblies. Then, we describe two different applications of electrospinning in service of cancer research: firstly, as three-dimensional (3D) fibrous materials for generating in vitro pre-clinical cancer models; and secondly, as patches encapsulating anticancer agents for in vivo delivery., 8 pages, 7 figures

Nanotechnology offers innovative tools for the design of biomimetic nanocarriers for targeted cancer therapy. These nano-systems present several advantages such as cargo’s protection and modulation of its release, inclusion of stimuli-responsive elements, and enhanced tumoral accumulation. All together, these nano-systems suffer low therapeutic efficacy in vivo because organisms can recognize and remove foreign nanomaterials. To overcome this important issue, different modifications on nanoparticle surfaces were exploited in order to reach the desired therapeutic efficacy eliciting, also, the response of immune system against cancer cells. For this reason, more recently, a new strategy involving cell membrane-covered nanoparticles for biomedical application has been attracting increasing attention. Membranes from red blood cells, platelets, leukocytes, tumor, and stem cells, have been exploited as biomimetic coatings of nanoparticles for evading clearance or stimulated immune system by maintaining in the same way their targeting capability. In this review, the use of different cell sources as coating of biomimetic nanocarriers for cancer therapy is discussed.

Summary of the ideaOur idea is focused on the development of “monoclonal-type” plastic antibodies based on Molecularly Imprinted Polymers (MIPs) able to selectively bind a portion of the novel coronavirus SARS-CoV-2 spike protein to block its function and, thus, the infection process. Molecular Imprinting, indeed, represents a very promising and attractive technology for the synthesis of MIPs characterized by specific recognition abilities for a target molecule. Given these characteristics, MIPs can be considered tailor-made synthetic antibodies obtained by a templating process.In the present study, the developed imprinted polymeric nanoparticles were characterized in terms of particles size and distribution by Dynamic Light Scattering (DLS) and the imprinting effect and selectivity were investigated by performing binding experiments using the receptor-binding domain (RBD) of the novel coronavirus and the RBD of SARS-CoV spike protein, respectively. Finally, the hemocompatibility of the prepared MIP-based plastic antibodies was also evaluated.

Background The ‘Primary HIV Prevention among Pregnant and Lactating Ugandan Women’ (PRIMAL) randomized controlled trial aimed to assess an enhanced counseling strategy linked to extended postpartum repeat HIV testing and enhanced counseling among 820 HIV-negative pregnant and lactating women aged 18–49 years and 410 of their male partners to address the first pillar of the WHO Global Strategy for the Prevention of Mother-to-Child HIV transmission (PMTCT). This paper presents findings of qualitative studies aimed at evaluating participants’ and service providers’ perceptions on the acceptability and feasibility of the intervention and at understanding the effects of the intervention on risk reduction, couple communication, and emotional support from women’s partners. Methods PRIMAL Study participants were enrolled from two antenatal care clinics and randomized 1:1 to an intervention or control arm. Both arms received repeat sexually transmitted infections (STI) and HIV testing at enrolment, labor and delivery, and at 3, 6, 12, 18 and 24 months postpartum. The intervention consisted of enhanced quarterly counseling on HIV risk reduction, couple communication, family planning and nutrition delivered by study counselors through up to 24 months post-partum. Control participants received repeat standard post-test counseling. Qualitative data were collected from intervention women participants, counsellors and midwives at baseline, midline and end of the study through 18 focus group discussions and 44 key informant interviews. Data analysis followed a thematic approach using framework analysis and a matrix-based system for organizing, reducing, and synthesizing data. Results At baseline, FGD participants mentioned multiple sexual partners and lack of condom use as the main risks for pregnant and lactating women to acquire HIV. The main reasons for having multiple sexual partners were 1) the cultural practice not to have sex in the late pre-natal and early post-natal period; 2) increased sexual desire during pregnancy; 3) alcohol abuse; 4) poverty; and 5) conflict in couples. Consistent condom use at baseline was limited due to lack of knowledge and low acceptance of condom use in couples. The majority of intervention participants enrolled as couples felt enhanced counselling improved understanding, faithfulness, mutual support and appreciation within their couple. Another benefit mentioned by participants was improvement of couple communication and negotiation, as well as daily decision-making around sexual needs, family planning and condom use. Participants stressed the importance of providing counselling services to all couples. Conclusion This study shows that enhanced individual and couple counselling linked to extended repeat HIV and STI testing and focusing on HIV prevention, couple communication, family planning and nutrition is a feasible and acceptable intervention that could enhance risk reduction programs among pregnant and lactating women. Trial registration ClinicalTrials.gov registration number NCT01882998, date of registration 21st June 2013.

Background Since the declaration of the 10th Ebola Virus Disease (EVD) outbreak in DRC on 1st Aug 2018, several neighboring countries have been developing and implementing preparedness efforts to prevent EVD cross-border transmission to enable timely detection, investigation, and response in the event of a confirmed EVD outbreak in the country. We describe Uganda’s experience in EVD preparedness. Results On 4 August 2018, the Uganda Ministry of Health (MoH) activated the Public Health Emergency Operations Centre (PHEOC) and the National Task Force (NTF) for public health emergencies to plan, guide, and coordinate EVD preparedness in the country. The NTF selected an Incident Management Team (IMT), constituting a National Rapid Response Team (NRRT) that supported activation of the District Task Forces (DTFs) and District Rapid Response Teams (DRRTs) that jointly assessed levels of preparedness in 30 designated high-risk districts representing category 1 (20 districts) and category 2 (10 districts). The MoH, with technical guidance from the World Health Organisation (WHO), led EVD preparedness activities and worked together with other ministries and partner organisations to enhance community-based surveillance systems, develop and disseminate risk communication messages, engage communities, reinforce EVD screening and infection prevention measures at Points of Entry (PoEs) and in high-risk health facilities, construct and equip EVD isolation and treatment units, and establish coordination and procurement mechanisms. Conclusion As of 31 May 2019, there was no confirmed case of EVD as Uganda has continued to make significant and verifiable progress in EVD preparedness. There is a need to sustain these efforts, not only in EVD preparedness but also across the entire spectrum of a multi-hazard framework. These efforts strengthen country capacity and compel the country to avail resources for preparedness and management of incidents at the source while effectively cutting costs of using a “fire-fighting” approach during public health emergencies.

Metabolic Syndrome is becoming more common and it is characterized by an excess intake of energy, readily available carbohydrates and fats that result in postprandial hyperglycemia and hyperlipidemia. In the treatment of Metabolic Syndrome, a diet characterized by functional food, high fiber intake and low glycemic index is recommended. The aim of this research was to study in vitro the beneficial and biological properties of black rice cultivated in Sibari plain, a particular area of the region of Calabria, and verify if the climatic conditions of this area influence the composition of this pigmented rice. The antioxidant activity was investigated by performing the DPPH radical scavenging assay, while the free phenolic content of CBR extract was measured by Folin Ciocalteu’s assay and the obtained results were expressed as mg of gallic acid equivalent/ mg of extract. In order to establish the anti-inflammatory effect of CBR extract, its reactivity towards nitric oxide (NO) was evaluated, while, its anti-hypertensive activity was studied by determining the ACE activity inhibition. CBR extract suppress, also, pancreatic lipase activity with an IC50 value of 34.3 µg/ml and it decreases cellular lipid accumulation by about 60%. Finally, its hypoglycemic effect was evaluated by measuring the inhibiting activity towards α-glucosidase and α-amylase enzymes. The obtained results demonstrate that this kind of black rice owns different beneficial properties, which make it a functional food that could improve metabolic disorders of MS.

Background Pathogenesis of Ebola virus disease remains poorly understood. We used concomitant determination of routine laboratory biomarkers and Ebola viremia to explore the potential role of viral replication in specific organ damage. Methods We recruited patients with detectable Ebola viremia admitted to the EMERGENCY Organizzazione Non Governativa Organizzazione Non Lucrativa di Utilita Sociale (ONG ONLUS) Ebola Treatment Center in Sierra Leone. Repeated measure of Ebola viremia, alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, creatine phosphokinase (CPK), lactate dehydrogenase (LDH), activated prothrombin time (aPTT), international normalized ratio (INR), creatinine, and blood urea nitrogen (BUN) were recorded. Patients were followed up from admission until death or discharge. Results One hundred patients (49 survivors and 51 nonsurvivors) were included in the analysis. Unadjusted analysis to compare survivors and nonsurvivors provided evidence that all biomarkers were significantly above the normal range and that the extent of these abnormalities was generally higher in nonsurvivors than in survivors. Multivariable mixed-effects models provided strong evidence for a biological gradient (suggestive of a direct role in organ damage) between the viremia levels and either ALT, AST, CPK LDH, aPTT, and INR. In contrast, no direct linear association was found between viremia and either creatinine, BUN, or bilirubin. Conclusions This study provides evidence to support that Ebola virus may have a direct role in muscular damage and imbalance of the coagulation system. We did not find strong evidence suggestive of a direct role of Ebola virus in kidney damage. The role of the virus in liver damage remains unclear, but our evidence suggests that acute severe liver injury is not a typical feature of Ebola virus disease.

Purpose Drug-induced sedation endoscopy (DISE) classification systems have been used to assess anatomical findings on upper airway obstruction, and decide and plan surgical treatments and act as a predictor for surgical treatment outcome for obstructive sleep apnoea management. The first objective is to identify if there is a universally accepted DISE grading and classification system for analysing DISE findings. The second objective is to identify if there is one DISE grading and classification treatment planning framework for deciding appropriate surgical treatment for obstructive sleep apnoea (OSA). The third objective is to identify if there is one DISE grading and classification treatment outcome framework for determining the likelihood of success for a given OSA surgical intervention. Methods A systematic review was performed to identify new and significantly modified DISE classification systems: concept, advantages and disadvantages. Results Fourteen studies proposing a new DISE classification system and three studies proposing a significantly modified DISE classification were identified. None of the studies were based on randomised control trials. Conclusion DISE is an objective method for visualising upper airway obstruction. The classification and assessment of clinical findings based on DISE is highly subjective due to the increasing number of DISE classification systems. Hence, this creates a growing divergence in surgical treatment planning and treatment outcome. Further research on a universally accepted objective DISE assessment is critically needed.

Drug-induced sedation endoscopy (DISE) classification systems play a significant role in clinical analysis based on DISE findings, treatment decision process, treatment planning process and fundamentally in treatment outcomes. However, there is a major problem: there is no universally agreed DISE classification system. Hence, for the same DISE examination different DISE classification systems can be used to: assess anatomic findings, decide and plan different treatments. Hence, this leads to different treatment outcomes. The key objective of this study is to propose uDISE model: universal drug-induced sedation endoscopy (DISE) classification system. Set theory and relational mapping was used to develop a DISE classification system based on anatomical structures/level; degree of severity; and configuration of obstruction and its relationship with existing DISE classification systems. uDISE model consists of seven anatomical sites (nose, velum, tonsils, lateral pharyngeal wall/oropharynx, tongue base, epiglottis and larynx), three degrees of obstructive severity (none, partial and complete), three configurations of obstruction (anteroposterior, lateral and circumferential) and a severity index. uDISE model was mapped to four existing DISE classification systems: Pringle and Croft grading system, VOTE, NOHL and P-T-L-Tb-E. uDISE model provides a methodology for mapping different DISE findings based on different classification systems into one common DISE assessments format. This provides a framework for comparing different DISE assessments, treatment plan and treatment outcome irrespective of DISE classification system used. Further research is required to establish a complete relational mapping between uDISE model and other existing DISE classification systems.

© 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Background: The Lancet Commission on Global Surgery established the Three Delays framework, categorising delays in accessing timely surgical care into delays in seeking care (First Delay), reaching care (Second Delay), and receiving care (Third Delay). Globally, knowledge gaps regarding delays for fracture care, and the lack of large prospective studies informed the rationale for our international observational study. We investigated delays in hospital admission as a surrogate for accessing timely fracture care and explored factors associated with delayed hospital admission. Methods: In this prospective observational substudy of the ongoing International Orthopaedic Multicenter Study in Fracture Care (INORMUS), we enrolled patients with fracture across 49 hospitals in 18 low-income and middle-income countries, categorised into the regions of China, Africa, India, south and east Asia, and Latin America. Eligible patients were aged 18 years or older and had been admitted to a hospital within 3 months of sustaining an orthopaedic trauma. We collected demographic injury data and time to hospital admission. Our primary outcome was the number of patients with open and closed fractures who were delayed in their admission to a treating hospital. Delays for patients with open fractures were defined as being more than 2 h from the time of injury (in accordance with the Lancet Commission on Global Surgery) and for those with closed fractures as being a delay of more than 24 h. Secondary outcomes were reasons for delay for all patients with either open or closed fractures who were delayed for more than 24 h. We did logistic regression analyses to identify risk factors of delays of more than 2 h in patients with open fractures and delays of more than 24 h in patients with closed fractures. Logistic regressions were adjusted for region, age, employment, urban living, health insurance, interfacility referral, method of transportation, number of fractures, mechanism of injury, and fracture location. We further calculated adjusted relative risk (RR) from adjusted odds ratios, adjusted for the same variables. This study was registered with ClinicalTrials.gov, NCT02150980, and is ongoing. Findings: Between April 3, 2014, and May 10, 2019, we enrolled 31 255 patients with fractures, with a median age of 45 years (IQR 31–62), of whom 19 937 (63·8%) were men, and 14 524 (46·5%) had lower limb fractures, making them the most common fractures. Of 5256 patients with open fractures, 3778 (71·9%) were not admitted to hospital within 2 h. Of 25 999 patients with closed fractures, 7141 (27·5%) were delayed by more than 24 h. Of all regions, Latin America had the greatest proportions of patients with delays (173 [88·7%] of 195 patients with open fractures; 426 [44·7%] of 952 with closed fractures). Among patients delayed by more than 24 h, the most common reason for delays were interfacility referrals (3755 [47·7%] of 7875) and Third Delays (cumulatively interfacility referral and delay in emergency department: 3974 [50·5%]), while Second Delays (delays in reaching care) were the least common (423 [5·4%]). Compared with other methods of transportation (eg, walking, rickshaw), ambulances led to delay in transporting patients with open fractures to a treating hospital (adjusted RR 0·66, 99% CI 0·46–0·93). Compared with patients with closed lower limb fractures, patients with closed spine (adjusted RR 2·47, 99% CI 2·17–2·81) and pelvic (1·35, 1·10–1·66) fractures were most likely to have delays of more than 24 h before admission to hospital. Interpretation: In low-income and middle-income countries, timely hospital admission remains largely inaccessible, especially among patients with open fractures. Reducing hospital-based delays in receiving care, and, in particular, improving interfacility referral systems are the most substantial tools for reducing delays in admissions to hospital. Funding: National Health and Medical Research Council of Australia, Canadian Institutes of Health Research, McMaster Surgical Associates, and Hamilton Health Sciences.

- Label: OBJECTIVES NlmCategory: OBJECTIVE content: A Demographic and Health Platform was established in Magude in 2015, prior to the deployment of a project aiming to evaluate the feasibility of malaria elimination in southern Mozambique, named the Magude project. This platform aimed to inform the design, implementation and evaluation of the Magude project, through the identification of households and population; and the collection of demographic, health and malaria information. - Label: SETTING NlmCategory: METHODS content: Magude is a rural district of southern Mozambique which borders South Africa. It has nine peripheral health facilities and one referral health centre with an inpatient ward. - Label: INTERVENTION NlmCategory: METHODS content: "A baseline census enumerated and geolocated all the households, and their resident and non-resident members, collecting demographic and socio-economic information, and data on the coverage and usage of malaria control tools. Inpatient and outpatient data during the 5\xE2\x80\x89years (2010 to 2014) before the survey were obtained from the district health authorities. The demographic platform was updated in 2016." - Label: RESULTS NlmCategory: RESULTS content: "The baseline census conducted in 2015 reported 48\xE2\x80\x89448 (92.1%) residents and 4133 (7.9%) non-residents, and 10\xE2\x80\x89965 households. Magude's population is predominantly young, half of the population has no formal education and the main economic activities are agriculture and fishing. Houses are mainly built with traditional non-durable materials and have poor sanitation facilities. Between 2010 and 2014, malaria was the most common cause of all-age inpatient discharges (representing 20% to 40% of all discharges), followed by HIV (12% to 22%) and anaemia (12% to 15%). In early 2015, all-age bed-net usage was between 21.8% and 27.1%\xE2\x80\x89and the reported coverage of indoor residual spraying varied across the district between 30.7% and 79%." - Label: CONCLUSION NlmCategory: CONCLUSIONS content: This study revealed that Magude has limited socio-economic conditions, poor access to healthcare services and low coverage of malaria vector control interventions. Thus, Magude represented an area where it is most pressing to demonstrate the feasibility of malaria elimination. - Label: TRIAL REGISTRATION NUMBER NlmCategory: BACKGROUND content: NCT02914145; Pre-results.

Background: In cancer research, studying cell motility is fundamental to investigate cancer invasion and drug resistance. In solid tumors constituted by a huge stroma component, such as pancreatic ductal adenocarcinoma (PDAC), the ability to quantify cell movement and interactions is mandatory to better understand the complex crosstalk between cancer and stroma cells. In PDAC, the pancreatic stellate cells (PSCs) are the principal source of dense fibrotic stroma: these closely interact with the PDAC cells to create a facilitating tumor microenvironment that supports local and distant tumor progression through the secretion and/or the response to a number of cytokines that globally increase cancer invasiveness; moreover, the dense tumor microenvironment contributes to resistance to chemotherapy and radiation therapy. Recent studies have established that targeting the stromal compartment in PDAC may lead to promising outcomes. Unfortunately, significant improvements in the overall survival of patients have not been realized in more than four decades, in part because of the lack of relevant preclinical models. Methods: To infer interactions existing between stromal and cancer cells in complex 3D environments, we developed a novel platform that combines time-lapse fluorescence microscopy, automated image detection, and extensive statistical analysis. To better mimic in situ PDAC, we created a hydrogel-based (Matrigel, collagen) model that allows cell tracking in 4 dimensions (x, y, z, t), not possible in 2D, using a mixed population of L3.6PL pancreatic cancer cells and PSCs at a ratio of 25% and 75%, respectively. To precisely identify the two populations and facilitate automatic cell detection, cells were transfected with GFP and mCherry vectors. Once in the 3D conformation, the cocultures were monitored through time-lapse confocal microscopy (CLSM) in controlled conditions, and the dataset containing the temporal evolution of the cells was processed by statistical tools. Results: Key to our approach was the generation of new machine learning-driven automated inferential protocols that resulted in the high-resolution imaging of the strength of the interactions between cells, as well as the potential presence of local chemokine gradients. In our ongoing studies, both commercial PDAC cell lines and pancreatic stellate cells were used to establish the model system. We are currently adopting the model to take full advantage of patient-derived PDAC cells established using the conditionally reprogrammed cells technique, mixed with patient-matched stellate cells. Since cell migration is a hallmark of cancer, we believe that this platform could be used as a reliable and reproducible approach for studying single-cell migration and invasion also in patient-derived models. The research leading to these results received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement No. 759959, ERC-StG “INTERCELLMED”). Citation Format: Marta Maria Cavo, Francesco Alemanno, Donatella Delle Cave, Eliana D'Amone, Adriano Barra, Enza Lonardo, Erika Parasido, Chris Albanese, Loretta Laureana del Mercato. Quantifying stroma-tumor cell interactions in three-dimensional cell culture systems [abstract]. In: Proceedings of the AACR Special Conference on the Evolving Landscape of Cancer Modeling; 2020 Mar 2-5; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2020;80(11 Suppl):Abstract nr A48.

Background: A great number of therapeutic limitations, such as chemoresistance, high dosage, and long treatments, are still present in cancer therapy, and are often followed by side effects such as infections, which represent the primary cause of death among patients. Methods: We report pH- and enzymatic-responsive hybrid clustered nanoparticles (HC-NPs), composed of a PCL polymeric core loaded with an anticancer drug, such as Imatinib Mesylate (IM), and coated with biodegradable multilayers embedded with antibacterial and anticancer baby-ship silver NPs, as well as a monoclonal antibody for specific targeting of cancer cells conjugated on the surface. Results: The HC-NPs presented an onion-like structure that serially responded to endogenous stimuli. After internalization into targeted cancer cells, the clustered nanoparticles were able to break up, thanks to intracellular proteases which degraded the biodegradable multilayers and allowed the release of the baby-ship NPs and the IM loaded within the pH-sensible polymer present inside the mothership core. In vitro studies validated the efficiency of HC-NPs in human chronic leukemic cells. This cellular model allowed us to demonstrate specificity and molecular targeting sensitivity, achieved by using a combinatorial approach inside a single nano-platform, instead of free administrations. The combinatory effect of chemotherapic drug and AgNPs in one single nanosystem showed an improved cell death efficacy. In addition, HC-NPs showed a good antibacterial capacity on Gram-negative and Gram-positive bacteria. Conclusions: This study shows an important combinatorial anticancer and antimicrobial effect in vitro.

Background Child mortality due to pneumonia is a major global health problem and is associated with hypoxemia. Access to safe and continuous oxygen therapy can reduce mortality; however, low-income countries may lack the necessary resources for oxygen delivery. We have previously demonstrated proof-of-concept that solar-powered oxygen (SPO2) delivery can reliably provide medical oxygen remote settings with minimal access to electricity. This study aims to demonstrate the efficacy of SPO2 in children hospitalized with acute hypoxemic respiratory illness across Uganda. Methods Objectives: Demonstrate efficacy of SPO2 in children hospitalized with acute hypoxemic respiratory illness. Study design: Multi-center, stepped-wedge cluster-randomized trial. Setting: Twenty health facilities across Uganda, a low-income, high-burden country for pediatric pneumonia. Site selection: Facilities with pediatric inpatient services lacking consistent O2 supply on pediatric wards. Participants: Children aged Randomization methods: Random installation order generated a priori with allocation concealment. Study procedure: Patients receive standard of care within pediatric wards with or without SPO2 system installed. Outcome measures: Primary: 48-h mortality. Secondary: safety, efficacy, SPO2 system functionality, operating costs, nursing knowledge, skills, and retention for oxygen administration. Statistical analysis of primary outcome: Linear mixed effects logistic regression model with 48-h mortality (dependent variable) as a function of SPO2 treatment (before versus after installation), while adjusting for confounding effects of calendar time (fixed effect) and site (random effect). Sample size: 2400 patients across 20 health facilities, predicted to provide 80% power to detect a 35% reduction in mortality after introduction of SPO2, based on a computer simulation of > 5000 trials. Discussion Overall, our study aims to demonstrate mortality benefit of SPO2 relative to standard (unreliable) oxygen delivery. The innovative trial design (stepped-wedge, cluster-randomized) is supported by a computer simulation. Capacity building for nursing care and oxygen therapy is a non-scientific objective of the study. If successful, SPO2 could be scaled across a variety of resource-constrained remote or rural settings in sub-Saharan Africa and beyond. Trial registration Clinicaltrials.gov, NCT03851783. Registered on 22 February 2019.

We present a histologically proven mucinous adenocarcinoma of the colon in a 40 year old female from Gulu, Northern Uganda. Her elder sister died at 25 years with advanced adenocarcinoma of colon similarly with her mother who died of the same illness 10 years apart. Using the Amsterdam criteria for the diagnosis of the carcinoma of the colon, this is descriptive of Hereditary Non Polyposis Colorectal Carcinoma (HNPCC). Blood examinations revealed microcytic hypochromic anaemia. The Renal and Liver function parameters were essentially normal. The abdominal ultrasonography showed an ill-defined mass in the right hypochondrial region which was heterogeneous with central echogenicity approximately 7.2cm wide and with no intra-abdominal lymphadenopathy or ascitis. At laparotomy, the sonographic findings were confirmed with a demonstrable mass in the hepatic flexure of the colon with hyperemic areas on its serosa. Macroscopically, there was an annular fungating mass with a central necrosis in the hepatic flexure measuring over 7.0cm. Histology of the colonic tumour showed a mucinous adenocarcinoma of the colon (Duke's B). This finding highlights the occurrence of colonic adenocarcinoma in the young person in Northern Uganda, a finding which draws the attention of the medical community towards having a higher index of suspicion for carcinoma of the colon in patients with similar presentation.

Background: A hallmark of glioblastoma is represented by their ability to widely disperse throughout the brain parenchyma. The importance of developing new anti-migratory targets is critical to reduce recurrence and improve therapeutic efficacy. Methods: Polydimethylsiloxane substrates, either mechanically uniform or presenting durotactic cues, were fabricated to assess GBM cell morphological and dynamical response with and without pharmacological inhibition of NNMII contractility, of its upstream regulator ROCK and actin polymerization. Results: Glioma cells mechanotactic efficiency varied depending on the rigidity compliance of substrates. Morphologically, glioma cells on highly rigid and soft bulk substrates displayed bigger and elongated aggregates whereas on durotactic substrates the same cells were homogeneously dispersed with a less elongated morphology. The durotactic cues also induced a motility change, cell phenotype dependent, and with cells being more invasive on stiffer substrates. Pharmacological inhibition of myosin or ROCK revealed a rigidity-insensitivity, unlike inhibition of microfilament contraction and polymerization of F-actin, suggesting that alternative signalling is used to respond to durotactic cues. Conclusions: The presence of a distinct mechanical cue is an important factor in cell migration. Together, our results provide support for a durotactic role of glioma cells that acts through actomyosin contractility to regulate the aggressive properties of GBM cells.

REALITY was funded by the Joint Global Health Trials Scheme (JGHTS) of the UK Department for International Development, the Wellcome Trust, and Medical Research Council (MRC) (grant number G1100693). Additional funding support was provided by the PENTA Foundation and core support to the MRC Clinical Trials Unit at University College London (grant numbers MC_UU_12023/23 and MC_UU_12023/26). Cipla Ltd, Gilead Sciences, ViiV Healthcare/GlaxoSmithKline, and Merck Sharp & Dohme donated drugs for REALITY, and ready-to-use supplementary food was purchased from Valid International. A. J. P. is funded by the Wellcome Trust (grant number 108065/Z/15/Z). J. A. B. is funded by the JGHTS (grant number MR/M007367/1). The Malawi-Liverpool–Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine (grant number 101113/Z/13/Z) and the Kenya Medical Research Institute (KEMRI)/Wellcome Trust Research Programme, Kilifi (grant number 203077/Z/16/Z) are supported by strategic awards from the Wellcome Trust, United Kingdom. Permission to publish was granted by the Director of KEMRI. This supplement was supported by funds from the Bill & Melinda Gates Foundation. Background. Severely immunocompromised human immunodefciency virus (HIV)-infected individuals have high mortality shortly afer starting antiretroviral therapy (ART). We investigated predictors of early mortality and "late presenter" phenotypes. Methods. Te Reduction of EArly MortaLITY (REALITY) trial enrolled ART-naive adults and children =5 years of age with CD4 counts .1). Results. Among 1711 included participants, 203 (12%) died. Mortality was independently higher with older age; lower CD4 count, albumin, hemoglobin, and grip strength; presence of World Health Organization stage 3/4 weight loss, fever, or vomiting; and problems with mobility or self-care at baseline (all P

This study aimed to assess HbA1c performance against single fasting blood glucose (FBG) for diagnosis of undiagnosed type 2 diabetes (T2D) and impaired fasting glycaemia (IFG) among general medical outpatients in Botswana. Participants aged, ≥20 years were cross-sectionally surveyed from August to October, 2014. All the participants underwent testing for HbA1c and FBG. The HbA1c sensitivity, specificity and predictive values in the diagnosis of T2D and IFG were computed and their Pearson’s correlation and scatter diagrams determined. A total of 291 participants (74.2% women) with a mean age of 50.1±11.0 years provided data for the current analysis. HbA1c at cut-off of ≥ 6.5% (48 mmol/mol) had a sensitivity and specificity for T2D of 100 (15.81 to 100.00) and 86.3% (86.16 to 89.92), respectively. Similarly, for IFG, the sensitivity and specificity was 100 (2.5 to 100) and 36.3% (30.3 to 42.6), respectively. The positive predictive value (PPV) was 4.8 (0.58 to 16.16) and 0.6% (0.02 to 3.45) for T2D and IFG screening, respectively. The negative predictive value (NPV) was 100% in both cases of T2D and IFG screening. HbA1c had a modest, positive correlation (r) with FBG for the overall population (r = 0.536, p < 0.001); for women, (r = 0 .578, p < 0.001) and men (r =0 .336, p =0.003). HbA1c had high sensitivity but widely varying specificity, high proportion of discordant results and poor prediction of T2D and IFG in this setting. Although, HbA1c correlation with fasting glucose was modest, both tests are required to improve diagnostic reliability in asymptomatic T2D screening program. Key words: Diabetes screening, HbA1c test, Botswana.

Osteosarcomas are highly malignant tumors, which develop rapid growth and local infiltration, inducing metastases that spread primarily in the lung. Treatment of these tumors is mainly based on pre- and post-operative chemotherapy and surgery of the primary tumor. Surgical resection though, generates bone defects. Reparation of these weaknesses presents formidable challenges to orthopedic surgery. Medicine regenerative grafts that act as both tumor therapy with constant local drug delivery and tissue regeneration may provide a new prospect to address this need. These implants can provide sustained drug release at the cancer area, decreasing systemic second effects such as inflammation, and a filling of the resected tissues with regenerative biomaterials. In this study microporous poly-ε-caprolactone (PCL) scaffolds have been developed for sustained local release of anti-inflammatory drug dexamethasone (DXM), used as drug model, in cancer medicine regenerative field. The microporous PCL matrix of the scaffolds supported the attachment, proliferation and osteogenic differentiation of osteoblast-like cells, while the polyelectrolyte multilayers, anchored to the inner pore surfaces, sustained locally DXM release. These microporous scaffolds demonstrate the ability to deliver DXM as a localized tumor therapy and to promote proliferation and differentiation of osteoblast-like cells in vitro.

BackgroundThe 'Primary HIV Prevention among Pregnant and Lactating Ugandan Women' (PRIMAL) study aimed to assess the effectiveness of an enhanced HIV counseling intervention for preventing HIV acquisition among HIV-uninfected mothers during pregnancy and throughout the breastfeeding period.MethodsWe conducted an unblinded randomized control trial between 22 February 2013 and 22 April 2016 to assess the effectiveness of an extended repeat HIV testing and enhanced counseling (ERHTEC) intervention aimed at preventing primary HIV infection among HIV-uninfected pregnant and lactating women in Uganda. HIV-uninfected pregnant women aged 15-49 were enrolled 1:1 individually or in couples together with their partner. Enrolled women and couples were randomized 1:1 to an intervention (ERHTEC) or control (extended repeat HIV testing and standard counseling) group and followed up to 24 months postpartum or six weeks past complete cessation of breastfeeding, whichever came first. Both groups were tested for sexually transmitted infections (STIs) and HIV at enrollment, delivery, 3 and 6 months postpartum and every 6 months thereafter until the end of follow-up. The intervention group received enhanced HIV prevention counseling every 3 months throughout follow-up. The control group received standard counseling at the time of HIV retesting. Both intervention and control couples were offered couple HIV testing and counseling at all study visits.Main outcome measuresFrequency of condom use and incidence of HIV, syphilis, gonorrhea, chlamydia and trichomoniasis over follow-up.ResultsBetween February 2013 and April 2014, we enrolled 820 HIV-uninfected pregnant women presenting for antenatal care individually (n = 410) or in couples (n = 410 women and 410 partners) in one urban and one rural public Ugandan hospital. Women's median age was 24 years (IQR 20-28 years). At baseline, participants did not differ in any socio-demographic, reproductive health, HIV testing history, sexual behavior, medical history or STI status characteristics; 96% (386/402) of couples were tested and counseled for HIV together with their partners at enrolment, 2.1% (7/329) of whom were found to be HIV-infected. Six hundred twenty-five (76%) women completed follow-up as per protocol (S1 Protocol). Women were followed for an average of 1.76 years and cumulated 1,439 women-years of follow-up or 81% of the maximum 1,779 women-years of follow-up assuming no dropouts. Men were followed for an average of 1.72 years. The frequency of consistent condom use and the proportion of women who used condoms over the last 3 months or at last vaginal sex increased substantially over follow-up in both arms, but there were no statistically significant differences in increases between the intervention and control arms. During follow-up, on average 42% (range 36%-46%) of couple partners were counseled together. Between 3.8% and 7.6% of women tested positive at any follow-up visit for any STI including syphilis, gonorrhea, C. trachomatis or T. vaginalis. Four women (two in each arm) and no enrolled men became infected with HIV, representing an overall HIV incidence rate of 0.186 per 100 person-years. Three of the women seroconverters had enrolled individually, one as a couple. At or before seroconversion, all four women reported their partners had extramarital relationships and/or had not disclosed their suspected HIV-infected status. There were no statistically significant differences between study arms for STI or HIV incidences.ConclusionsA sustained enhanced HIV prevention counseling intervention for up to 2 years postpartum among pregnant and breastfeeding women did not have a statistically significant effect on condom use or HIV incidence among these women. However, in both study arms, condom use increased over follow-up while STI and HIV incidence remained very low when compared to similar cohorts in and outside Uganda, suggesting that repeat HIV testing during breastfeeding, whether with enhanced or standard counseling, may have had an unintended HIV preventive effect among pregnant and lactating women in this setting. Further research is needed to verify this hypothesis.Trial registrationClinicalTrials.gov NCT01882998.

Glioblastoma (GBM), or grade IV glioma, is an extremely aggressive tumor that infiltrates through the brain leaving the patient with a median survival time from 12 to 15 months (Ostrom et al., 2013). Individual aspects of the microenvironment features play a critical role on GBM cell dynamics and treatment resistance (Bellail et al., 2004; Zamecnik, 2005; Calabrese et al., 2007). Because of GBM's aggressive and invasive behavior, inhibition of GBM migration is envisaged as an important therapeutic objective (Bravo-Cordero et al., 2012; Wells et al., 2013). However, current models fail to account for the complex brain microenvironment. The demand of preclinical models that can faithfully mimic the clinical scenario may bridge the discrepancy between preclinical and clinical data and aid to develop treatments that are more effective. The extracellular matrix (ECM) of the GBM microenvironment is constitutively composed of the polysaccharide hyaluronic acid (HA), and in a distinctive minor degree of tenascin-C, collagen IV and V, fibronectin, and laminin (Giese and Westphal, 1996; Rape et al., 2014). Also, typically with high glioma grade, the HA's cellular receptor CD44 is overexpressed, suggesting that CD44-enriched cells invade more efficiently the brain parenchyma (Bellail et al., 2004). GBM malignancy is furthermore promoted through interactions with the other aforementioned ECM components through different biochemical pathways (Sarkar et al., 2006; Lathia et al., 2012), which trigger an increase of the concentration of the non-cellular components (Bellail et al., 2004; Lathia et al., 2012). This increased density of the tumor ECM consequently increases the mechanical stiffness of the microenvironment (Ananthanarayanan et al., 2011; Wiranowska and Rojiani, 2011; Pathak and Kumar, 2012; Pedron and Harley, 2013; Kim and Kumar, 2014; Umesh et al., 2014; Heffernan et al., 2015). In our opinion, to gain further insights into tumor invasiveness, heterogeneity and treatment resistance, we have to look more deeply at how cell behavior is influenced by matrix stiffness (a process known as mechanotaxis or durotaxis) (Lo et al., 2000; Cortese et al., 2009; Palama et al., 2012, 2016).

Chronic myeloid leukaemia (CML) is caused by the BCR-ABL oncogene, which encodes the constitutively active BCR-ABL tyrosine kinase. Targeted therapy with tyrosine-kinase inhibitors induces a partial cytogenetic response in most patients. Nanosystems can represent an opportunity for combinatorial therapy with the capacity to simultaneously release different therapeutic agents, checking the pharmacokinetic properties. In this work, we have developed a novel poly-(ε-caprolactone) (PCL) nanosystem for combinatorial therapy in CML, composed of a biodegradable pH sensitive core releasing Nilotinib (Nil) and an enzymatic sensitive outer shell releasing Imatinib Mesylate (IM), resulting in wool-like nanoparticles (NPs). The resulting double loaded wool-like hollow PCL NPs showed a high dual-drug encapsulation efficiency, pH and enzymatic sensitivity and synchronized drug release capability. The combinatorial delivery of IM and Nil exhibited an importantly reduced IC50 value of IM and Nil on leukaemia cells compared to single free drugs administration. In vitro results, showed that combinatorial nanomixures preserved the biological activity of loaded drugs for extensive time windows and led to a constant release of active drug. In addition, the combination of IM and Nil in single PCL NPs have shown a more therapeutic efficiency at a low dose with respect to the single drug nanomixures, confirming that both drugs reached the target cell precisely, maximizing the cytotoxicity while minimizing the chances of cell resistance to drugs.

Bio-nanomaterials offer promise in the field of tissue engineering. Specifically, environmental cues such as the material chemistry, topography and rigidity of the surface to which cells adhere to, can alter and dictate cell shape, proliferation, migration, and gene expression. How deeply each factor (topographical, chemical and mechanical) drives cell response remains incompletely understood. To illustrate cell sensitivities to different factors, we herein present ZnO nanorods (ZnO-Nrds) coated on glass and polydimethylsiloxane (PDMS) substrates and analyzed cell viability and proliferation. The work presented here shows a clear response of various cell lines (mouse embryonic fibroblasts 3T3, human cervix carcinoma HeLa and human osteoblast-like cells MG63) to the rigidity of the underlying surface. The chemical counterpart, given by the presence of ZnO-Nrds, strongly reduced the cell viability of all cell lines. However, the substrate underlying the ZnO coating impacted cell spreading and viability. The substrates exhibited a better ability to neglect cell attachment and proliferation with the ZnO coating and pro-apoptoticity specifically with the PDMS as the underlying substrate which exhibited a "softer" environment with respect to a glass substrate. The results also revealed that the few cells that adhered to the ZnO-Nrds on PDMS and glass showed a rounded morphology. On the basis of these observations, we can correlate common features of phenomenological cell response to chemotactic and durotactic cues. The work presented herein reinforces the response of cells to changes in substrate rigidity. These observations provide a foundation for a potentially promising approach to decrease cell adhesion and thus as an optimal substrate for different applications such as prosthesis design, tissue engineering, anti-bio fouling materials and diagnostics.

There is an exponential growing attention in developing new micro/nano-delivery systems for controlled delivery of bioactive agents, to control cellular functions modulation in a more effective manner. In this study, the effect of dexamethasone encapsulated in calcium carbonate microcubes on proliferation and osteogenic activity of human osteoblasts in vitro was investigated. Dexamethasone-loaded calcium carbonate microcubes are suggested for supportive controlled release and improving osteogenic activity of low dose of dexamethasone. The calcium carbonate microcubes have a cubic structure of about 2 µm and represent a good performance in molecular delivery systems for bone tissue engineering thanks to their potential to mimic the composition, structure, and properties of native bone. The presence of polyelectrolyte multilayers that covered the calcium carbonate microcubes allowed to modulate the release kinetics of active dexamethasone over time. Our dexamethasone-loaded calcium carbonate microcubes provide a simple and easy way to allow controlled release of dexamethasone or other active agents in scaffolds for bone tissue engineering applications.

Lycium barbarum (Goji) fruits are mainly cultivated in northwestern China and are well known for their beneficial and healthy effects. In this work, the biological and functional properties of Calabrian Goji extract, obtained from Goji berries cultivated in the Sibari Plain (in the Italian region of Calabria), were demonstrated. In order to evaluate the use of this extract as a food supplement for cognitive and mental disorders, the quantification of Carotenoids as Zeaxanthin equivalents was made. The antioxidant activity was investigated by evaluating the scavenging properties against 2,2′-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-Azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radicals and by performing the ORAC (Oxygen Radical Absorbance Capacity) assay. The inhibition of lipid peroxidation was quantified by bleaching test and the ability to inhibit acetylcholinesterase enzyme and to scavenge nitric oxide radical was also evaluated. All the results were compared to those obtained from a Chinese Goji extract used as a reference. Based on the reported data, Calabrian Goji might be used as a food supplement with a possible application in cognitive disorders, mental impairments and other neurodegenerative diseases, due to its biological properties and the high levels of Carotenoids.

Accreditation of laboratories is one means to promote quality laboratory services, underscoring the need to document factors that facilitate laboratory accreditation. A desk review and key informant’s interviews were conducted to determine the roles of country leadership and policies in laboratory accreditation. Overall, the review revealed that Uganda has enabling factors for laboratory accreditation, putting the country in a state of accreditation-readiness and including strong leadership that provides stewardship and availability of a national health laboratory policy with an explicit statement on laboratory accreditation. A National Laboratory Technical and Policy Committee coordinated the development of the policy. Laboratory training schools provide leadership in training laboratory professionals, while the Association of Medical Laboratory Technologists provides professional leadership. Although there is no national accreditation system, some laboratories are participating in international laboratory accreditation. Key informants expressed strong support for and observed that laboratory accreditation is beneficial and can be implemented in Uganda. Lessons from this study can benefit countries planning to implement laboratory accreditation. Countries that have not developed national laboratory policies and strategic plans should do so to guide the strengthening of laboratory systems and services as a part of health systems strengthening, which would be a springboard for laboratory accreditation.

Hair loss represents a condition that adversely affects the social life of patients. The most common cause is androgenetic alopecia (AGA), which is a genetically determined progressive hair-loss condition involving 5&alpha, reductase. In this study, a novel anti-baldness agent based on Interconnected PolymerS TeChnology (IPSTiC), which is an effective strategy for the delivery of bioactive molecules, was developed. This product (IPSTiC patch hair) is based on a polymeric blend consisting of high molecular weight hyaluronic acid and soybean proteins and is able to improve efficacy and stability of bioactive ingredients such as Origanum vulgare leaf extract, Camellia Sinensis leaf extract, and Capsicum Annuum fruit extract. The efficacy of the developed anti-baldness agent was investigated by performing several tests including NO radical and 5&alpha, reductase inhibition assays, stability studies under different conditions, and in vitro diffusion studies using Franz cells. The biocompatibility of IPSTiC patch hair was also evaluated by in vitro analysis of the pro-sensitising potential and EPISKIN model. The obtained results confirmed both the efficacy and safety of IPSTiC patch hair supporting the potential use of this product in the topical treatment of AGA.