Tuberculosis in prison: What about after release? The example of French Guiana.

INTRODUCTION: Tuberculosis is a major cause of mortality worldwide. Prisoners in Guiana have multiple risk factors. The primary objective of this study was to describe tuberculosis occurring in prison and after release in French Guiana between 2008 and 2020. Secondary objectives were to identify tuberculosis risk factors and determine annual incidences. METHODS: A retrospective cohort study of tuberculosis cases was carried out at the Guiana prison between 2008 and 2020. Data were collected from prison registers and cross-referenced with the list of tuberculosis notifications in French Guiana. RESULTS: A total of 36 cases of tuberculosis were studied. Incidence was high, at 263/100,000 per year, higher than elsewhere in France and comparable to that in Brazil. Despite visibly effective screening on entry, with little evidence of intra-prison circulation of tuberculosis, 39% of patients were diagnosed within two years of leaving prison (76% were symptomatic). This could be explained by the high prevalence of latent forms (LTI). DISCUSSION: Continued screening on entry, in combination with annual radiological and clinical screening, and reinforced follow-up on release seem indicated to improve patient management and the search for possible LTI.

Targeted Doxorubicin-Loaded Dendronized Gold Nanoparticles.

Dendronized nanoparticles, also called nanoparticle-cored dendrimers, combine the advantages of nanoparticles and dendrimers. These very stable and polyvalent nanoparticles can be used for diverse applications. One such application is drug delivery, because the dendrons can enhance the density of the payload. In this report, we describe the design of multifunctional gold nanoparticles (AuNPs) coated with poly(propylene imine) (PPI) dendrons that contain both prostate cancer active targeting and chemotherapeutic drugs. The PPI dendron is a good candidate for the design of drug delivery vehicles because of its ability to induce a proton sponge effect that will enhance lysosomal escape and intracellular therapeutic delivery. The chemotherapeutic drug used is doxorubicin (DOX), and it was linked to the dendron through a hydrazone acid-sensitive bond. Subsequent acidification of the AuNP system to a pH of 4-5 resulted in the release of 140 DOX drugs per nanoparticles. In addition, the PPI dendron was conjugated via "click" chemistry to an EphA2-targeting antibody fragment that has been shown to target prostate cancer cells. In vitro cell viability assays revealed an IC50 of 0.9 nM for the targeted DOX-bearing AuNPs after 48 h incubation with PC3 cells. These results are very promising upon optimization of the system.

Professional delays in referral of patients with mouth cancer: six case histories.

Professional delay is an important delay in referral of patients with suspected mouth cancer. Missing the possibility of cancer might not only result in worse outcomes in respect to function and survival, but also have medicolegal implications. The aim of this article was to review a consecutive cohort of patients over a two-year period with mouth cancer diagnosis and identify those with professional delay and illustrate the main types of presentations using short case histories. The multi-disciplinary team records were used to identify case notes of a two-year (2019 and 2020) consecutive cohort of patients diagnosed with mouth cancer, including referrals from primary and secondary care. Professional delay was considered if red flag symptoms were not referred within two weeks or if there was initial misdiagnosis. In total, 246 patients with mouth cancer were discussed with the multi-disciplinary team: 35 had delay in referral or misdiagnosis of mouth cancer. Six common scenarios were identified: 1) sudden onset paraesthesia; 2) dental abscess; 3) temporomandibular joint dysfunction syndrome (TMJD) and abscess; 4) TMJD; 5) trauma/facial fracture; and 6) non-healing socket following dental extraction. To conclude, it can be difficult to accurately diagnose mouth cancer in primary dental and medical care and an index of suspicion is essential in order to minimise the possibility of professional delay.

Modular and efficient synthesis of a poly (propylene imine) (PPI) dendron applied to acid-sensitive doxorubicin conjugation.

The shorter synthesis of a novel poly(propylene imine) (PPI) dendron that can be quantitatively conjugated in good yields in a modular fashion to various modified Michael acceptors is reported herein. The focal point of the PPI dendron was coupled to an ester-linked thioctic acid-modified spacer to allow for an improved scalable synthesis and to allow attachment to other suitable systems, such as nanoparticle surfaces. The two modified Michael acceptors reported here are an acyl hydrazine Michael acceptor as well as an azide Michael acceptor. The acyl hydrazine modified third generation PPI dendron was further conjugated to doxorubicin (DOX) as a model system to test acid-sensitive drug delivery. The PPI-DOX conjugate displayed fast release of DOX at pH 4.5 while remaining stable at pH 7.4 and the PPI-DOX conjugate showed low in vitro cytotoxicity against PC3 prostate cancer cells. This modular platform represents a powerful dendronized system for incorporation onto nanoparticles or other systems to allow for multifunctional drug delivery.

High incidence of acute Q fever among incarcerated people in Cayenne, French Guiana.

Q fever is a major public health problem in French Guiana. In recent years, a considerable number of cases has been reported in French Guiana's penitentiary center. The main objective of this study was to describe the epidemiology of these cases. A retrospective study was conducted at the prison to identify cases of acute Q fever in people incarcerated between 2010 and 2021. During the study period, 16 patients were diagnosed with acute Q fever. The positivity rate varied between 13 and 57%. The annual incidence rate in 2019, 2020 and 2021 was 269 (95% CI: 0-640) 1,120 (95% CI: 290-1950) and 1,931 (95% CI: 60-3810) per 100,000 person-years, respectively. While several vertebrate species have already been shown to play an important role in the transmission of Coxiella burnetii, the full epidemiology picture in the tropics is far from clear, and the prison context, with its controlled environment, could help provide answers.

Erythroblastic synartesis associated with lymphoproliferative disorder: There can be more than meets the eye.

Erythroblastic synartesis is a rare cause of acquired dyserythropoiesis. Only 9 cases have been previously reported. We hereby report 3 cases of patients diagnosed with erythroblastic synartesis associated with monoclonal immunoglobulin and an overt malignant lymphoid disorder. A different B-cell clone may produce the monoclonal immunoglobulin, forming a biclonal disorder. In light of these data and literature review, treatment targeting the paraprotein seems to be efficient to control synartesis and correct anemia. In the case of monoclonal gammapathy associated with chronic lymphocytic leukemia, therapeutics should be adapted to control both chronic lymphocytic leukemia and monitored monoclonal immunoglobulin titer.

High incidence of acute Q fever among incarcerated people in Cayenne, French Guiana

ABSTRACT Q fever is a major public health problem in French Guiana. In recent years, a considerable number of cases has been reported in French Guiana's penitentiary center. The main objective of this study was to describe the epidemiology of these cases. A retrospective study was conducted at the prison to identify cases of acute Q fever in people incarcerated between 2010 and 2021. During the study period, 16 patients were diagnosed with acute Q fever. The positivity rate varied between 13 and 57%. The annual incidence rate in 2019, 2020 and 2021 was 269 (95% CI: 0-640) 1,120 (95% CI: 290-1950) and 1,931 (95% CI: 60-3810) per 100,000 person-years, respectively. While several vertebrate species have already been shown to play an important role in the transmission of Coxiella burnetii, the full epidemiology picture in the tropics is far from clear, and the prison context, with its controlled environment, could help provide answers.

Sexual and reproductive health of incarcerated women in French Guiana: a qualitative approach.

PURPOSE: Incarcerated women are a vulnerable population in terms of sexual and reproductive health. In French Guiana, most incarcerated women come from unsafe environments and are incarcerated because of drug trafficking. Medical follow-up processes used in prison (medical assessment on arrival, and then two half-days per week upon request but without an obstetrician-gynecologist) does not allow for a thorough assessment of the impact of incarceration on women prisoners' health to take place. In the absence of data, the purpose of this study was to describe incarcerated women's experiences in relation to sexual and reproductive health. DESIGN/METHODOLOGY/APPROACH: Semi-structured interviews were conducted among French-speaking adult women who had been incarcerated for at least four months in a French Guianan prison. Menstruation, contraception, pregnancy, abortion, sexually transmitted infections and sexuality were described by means of interpretative phenomenological analysis. FINDINGS: A total of 14 women were interviewed. They suffered from menstrual cycle disorders, poor hygiene and menstrual insecurity. They appeared to have emotionally disinvested sexuality. However, intra-prison sexual activity existed for some (masturbation, conjugal prison visits, homosexual intercourse between fellow prisoners). Homosexual relations were a source of discrimination. Being pregnant while incarcerated was viewed negatively. A lack of knowledge about sexual and reproductive health and high-risk behaviors such as piercing and tattooing practices were widespread. ORIGINALITY/VALUE: Incarceration is a vulnerable time for women's sexual and reproductive health. Sexual activity exposes women to risks and discrimination that should be taken into account in a multidisciplinary approach adapted to the prison environment.

Nanoparticle Delivery in Prostate Tumors Implanted in Mice Facilitated by Either Local or Whole-Body Heating.

This work discusses in vivo experiments that were performed to evaluate whether local or whole-body heating to 40 °C reduced interstitial fluid pressures (IFPs) and enhanced nanoparticle delivery to subcutaneous PC3 human prostate cancer xenograft tumors in mice. After heating, 0.2 mL of a previously developed nanofluid containing gold nanoparticles (10 mg Au/mL) was injected via the tail vein. The induced whole-body hyperthermia led to increases in tumor and mouse body blood perfusion rates of more than 50% and 25%, respectively, while the increases were much smaller in the local heating group. In the whole-body hyperthermia groups, the IFP reduction from the baseline at the tumor center immediately after heating was found to be statistically significant when compared to the control group. The 1 h of local heating group showed IFP reductions at the tumor center, while the IFPs increased in the periphery of the tumor. The intratumoral gold nanoparticle accumulation was quantified using inductively coupled plasma mass spectrometry (ICP-MS). Compared to the control group, 1 h or 4 h of experiencing whole-body hyperthermia resulted in an average increase of 51% or 67% in the gold deposition in tumors, respectively. In the 1 h of local heating group, the increase in the gold deposition was 34%. Our results suggest that 1 h of mild whole-body hyperthermia may be a cost-effective and readily implementable strategy for facilitating nanoparticle delivery to PC3 tumors in mice.

Patient-reported outcome measures in hemodialysis patients: results of the first multicenter cross-sectional ePROMs study in France.

BACKGROUND: Kidney failure with replacement therapy and hemodialysis are associated with a decrease in quality of life (QOL). Self-reported QOL symptoms are not always prioritized by the medical team, potentially leading to conflicting priorities with patients. Electronic patient-reported outcome measures (ePROMs) allow physicians to better identify these symptoms. The objective was to describe the prevalence of symptoms self-reported by hemodialysis (HD) patients. METHODS: A multicenter cross-sectional study was conducted in three HD centers. Patients were included if they were 18 years old or over treated with HD for at least 3 months in a center. Data were collected by the patient via a self-administered ePROMs questionnaire. Data included patient characteristics, post-dialysis fatigue and intensity, recovery time after a session, perceived stress, impaired sleep the day before the dialysis session, current state of health and the change from the past year. A multivariate analysis was conducted to identify relations between symptoms. RESULTS: In total, we included 173 patients with a mean age of 66.2 years, a mean ± SD hemodialysis duration of 48.9 ± 58.02 months. The prevalence of fatigue was 72%. 66% had a high level of stress (level B or C). Recovery time was more than 6 h after a HD session for 25% of patients and 78% declared they had a better or unchanged health status than the previous year. Sleep disturbance was associated with cardiovascular comorbidities (OR 5.08 [95% CI, 1.56 to 16.59], p = 0.007). CONCLUSIONS: Fatigue and stress were the main symptoms reported by HD patients. The patient's care teams should better consider these symptoms.

Crotamine Cell-Penetrating Nanocarriers: Cancer-Targeting and Potential Biotechnological and/or Medical Applications.

Crotamine is a basic, 42-residue polypeptide from snake venom that has been shown to possess cell-penetrating properties. Here we describe the preparation, purification, biochemical and biophysical analysis of venom-derived, recombinant, chemically synthesized, and fluorescent-labeled crotamine. We also describe the formation and characterization of crotamine-DNA and crotamine-RNA nanoparticles; and the delivery of these nanoparticles into cells and animals. Crotamine forms nanoparticles with a variety of DNA and RNA molecules, and crotamine-plasmid DNA nanoparticles are selectively delivered into actively proliferating cells in culture or in living organisms such as mice, Plasmodium, and worms. As such, these nanoparticles could form the basis for a nucleic acid drug-delivery system. We also describe here the design and characterization of crotamine-functionalized gold nanoparticles, and the delivery of these nanoparticles into cells. We also evaluated the viability of using the combination of crotamine with silica nanoparticles in animal models, aiming to provide slow delivery, and to decrease the crotamine doses needed for the biological effects. In addition, the efficacy of administering crotamine orally was also demonstrated.

Impaired decision making following escalation of cocaine self-administration predicts vulnerability to relapse in rats.

Impairments in cost-benefit decision making represent a cardinal feature of drug addiction. However, whether these alterations predate drug exposure, thereby contributing to facilitating loss of control over drug intake, or alternatively arise as a result of drug use and subsequently confer vulnerability to relapse has yet to be determined. Male Sprague-Dawley rats were trained to self-administer (SA) cocaine during 19 daily long-access (12-h) sessions; conditions reliably shown to promote escalation. One week after cocaine SA, rats underwent an extinction/relapse test immediately followed by conditioned stimuli-, stress-, and drug-primed reinstatement challenges. The influence of escalated cocaine intake on decision making was measured over time by four test sessions of a rodent analogue of the Iowa Gambling Task (rGT), once prior to cocaine exposure and then 1 day, 1 week, and 1 month after the last SA session. Substantial individual variability was observed in the influence of escalated cocaine SA on decision-making performance. A subset of rats displayed pronounced deficits, while others showed unaffected or even improved performance on the rat Gambling Task (rGT) 24 hours after the last SA session. When challenged with a relapse test after 1 week of forced abstinence, animals that showed impaired decision making following SA displayed an increased propensity to respond for cocaine under extinction. These data suggest that decision-making deficits in individuals with drug addiction are not antecedent to-but arise as a consequence of-drug exposure. Moreover, these data indicate that susceptibility to the deleterious effects of drugs on decision making confers vulnerability toward relapse.

Set of Highly Stable Amine- and Carboxylate-Terminated Dendronized Au Nanoparticles with Dense Coating and Nontoxic Mixed-Dendronized Form.

The synthesis of a novel poly(propyleneimine) (PPI) dendron in gram scale as well as its use in the formation of a highly stable, dendronized gold nanoparticle (AuNP)-based drug delivery platform is described herein. The AuNP-based platform is composed of three complementary parts: (i) a 15 nm AuNP core, (ii) a heterofunctional thioctic acid-terminated tetraethylene glycol spacer, and (iii) a third-generation PPI dendron with a unique protonation profile and diverse end-group functionalization that allows for further derivatization. The prepared dendronized AuNPs are able to withstand several rounds of lyophilization cycles with no sign of aggregation, are stable in phosphate-buffered saline and Hanks' buffer as well as in serum, and are resistant to degradation by glutathione exchange reactions. This nanocarrier platform displays a dense coating, with >1400 dendrons/AuNPs, which will enable very high payload. Furthermore, while amine-terminated AuNPs expectedly showed cytotoxicity against the MCF-7 breast cancer cell line from a NP concentration of 1 nM, the mixed monolayer AuNPs (coated with 40/60 amine/carboxylate dendrons) interestingly did not exhibit any sign of toxicity at concentrations as high as 15 nM, similar to the carboxylate-terminated AuNPs. The described dendronized AuNPs address the current practical need for a stable NP-based drug delivery platform which is scalable and easily conjugable, has long-term stability in solution, and can be conveniently formulated as a powder and redispersed in desired buffer or serum.

Single nanomaterial level investigation of ZnO nanorod sulfidation reactions via position resolved confocal Raman spectroscopy.

Zinc oxide (ZnO) nanomaterials have been used as desulfurizing sorbents for gaseous streams, zinc sulfide (ZnS)-forming template lattices in nanomaterial synthesis, and agriculturally produced sulfur (S)-removing reagents from the environment. Although various nanoscale forms of ZnO have already been utilized widely for such purposes, there is currently a lack of fundamental insight into the sulfidation of ZnO nanomaterials at the single nanocrystal level. We demonstrate that position-resolved confocal Raman spectroscopy can be successfully used to reveal the sulfidation process of ZnO NRs occurring at the single nanomaterial level. We attained a single crystal level understanding of the facet-dependent sulfidation reactivity of ZnO NRs by tracking the same NRs with Raman spectroscopy before and after the sulfidation reaction and quantitatively analyzing various ZnS-induced phonon scattering intensities from different positions on the NRs. The trend in NR facet-dependent sulfidation reactivity is further substantiated by correlating it with the electron microscopy and fluorescence data measured from the same NRs. The insight obtained from this study may provide the much-needed fundamental knowledge base for designing optimal ZnO nanostructures beneficial to many technological and industrial applications exploiting the ZnO-to-ZnS conversion. Taken together with the well-established methods to synthesize ZnO nanomaterials of specific crystal shapes and structures, our findings from this study may be broadly applicable in formulating and optimizing more advanced, low-dimensional ZnO sorbents and scrubbers for highly effective S removal.

Strong coupling and induced transparency at room temperature with single quantum dots and gap plasmons.

Coherent coupling between plasmons and transition dipole moments in emitters can lead to two distinct spectral effects: vacuum Rabi splitting at strong coupling strengths, and induced transparency (also known as Fano interference) at intermediate coupling strengths. Achieving either strong or intermediate coupling between a single emitter and a localized plasmon resonance has the potential to enable single-photon nonlinearities and other extreme light-matter interactions, at room temperature and on the nanometer scale. Both effects produce two peaks in the spectrum of scattering from the plasmon resonance, and can thus be confused if scattering measurements alone are performed. Here we report measurements of scattering and photoluminescence from individual coupled plasmon-emitter systems that consist of a single colloidal quantum dot in the gap between a gold nanoparticle and a silver film. The measurements unambiguously demonstrate weak coupling (the Purcell effect), intermediate coupling (Fano interference), and strong coupling (Rabi splitting) at room temperature.

Controlled etching and tapering of Au nanorods using cysteamine.

While gold nanorods (AuNRs) have found many applications due to their unique optical properties, a few challenges persist in their synthesis. Namely, it is often difficult to reproducibly synthesize AuNRs with specific and monodisperse sizes, especially at shorter aspect ratios. Here, we report a method of post-synthesis precise tailoring of AuNRs by etching with cysteamine. Cysteamine selectively etches AuNRs from their ends while preserving the initial rod shape and monodispersity, making this a viable means of obtaining highly monodisperse short AuNRs down to aspect ratio 2.3. Further, we explore the effect of this etching method on two types of silica-coated AuNRs: silica side-coated and silica end-coated AuNRs. We find that the etching process is cysteamine concentration-dependent and can lead to different degrees of sharpening of the silica-coated AuNRs, forming elongated tips. We also find that cysteamine behaves only as a ligand at concentrations above 200 mM, as no etching of the AuNRs is observed in this condition. Simulations show that excitation of plasmon resonances in these sharpened AuNRs produces local electric fields twice as strong as those produced by conventional AuNRs. Thus, cysteamine etching of AuNRs is shown to be an effective means of tailoring both the size and shape of AuNRs along with their corresponding optical properties. At the same time, the resulting cysteamine coating on the etched AuNRs displays terminal amino groups that allow for further functionalization of the nanorods.

Dendronized Systems for the Delivery of Chemotherapeutics.

This chapter reviews the use of dendronized systems as nanocarriers for the delivery of chemotherapeutic drugs. Dendronized systems include dendrimers prepared through convergent methods as well as other systems containing dendrons (e.g., polymers, nanoparticles, liposomes). The preparation of such systems is detailed, followed by the various conjugation techniques used for the transport of chemotherapeutic drugs and their specific delivery to tumor cells. In addition, the ability of dendronized systems to provide passive and active targeting to tumors is discussed. The efficacy of drug delivery using dendronized systems is also illustrated through specific examples of kinetic and biological studies. Finally, the newest trends in conjugation of the most common chemotherapeutics to dendronized systems are described. Overall, this chapter highlights dendronized systems as a way to improve the therapeutic efficiency of drugs for the treatment of cancer. All the recent developments in areas, such as biodegradable dendrimers, modifications to enhance biocompatibility, selectively cleavable drug conjugations, ligand-mediated targeting, and the potential for multifunctional properties, show promises for future advances in cancer therapy.

Spatially Correlated, Single Nanomaterial-Level Structural and Optical Profiling of Cu-Doped ZnO Nanorods Synthesized via Multifunctional Silicides.

We demonstrate a straightforward and effective method to synthesize vertically oriented, Cu-doped ZnO nanorods (NRs) using a novel multipurpose platform of copper silicide nanoblocks (Cu3Si NBs) preformed laterally in well-defined directions on Si. The use of the surface-organized Cu3Si NBs for ZnO NR growth successfully results in densely assembled Cu-doped ZnO NRs on each NB platform, whose overall structures resemble thick bristles on a brush head. We show that Cu3Si NBs can uniquely serve as a catalyst for ZnO NRs, a local dopant source of Cu, and a prepatterned guide to aid the local assembly of the NRs on the growth substrate. We also ascertain the crystalline structures, optical properties, and spectroscopic signatures of the Cu-doped ZnO NRs produced on the NBs, both at each module of NRs/NB and at their ensemble level. Subsequently, we determine their augmented properties relative to the pristine form of undoped ZnO NRs and the source material of Cu3Si NBs. We provide spatially correlated structural and optical data for individual modules of Cu-doped ZnO NRs assembled on a Cu3Si NB by resolving them along the different positions on the NB. Ensemble-averaged versus individual behaviors of Cu-doped ZnO NRs on Cu3Si NBs are then compared. We further discuss the potential impact of such ZnO-derived NRs on their relatively unexplored biological and biomedical applications. Our efforts will be particularly useful when exploiting each integrated module of self-aligned, Cu-doped ZnO NRs on a NB as a discretely addressable, active element in solid-state sensors and miniaturized luminescent bioprobes.

Design and characterization of crotamine-functionalized gold nanoparticles.

This paper describes the development of a facile and environmentally friendly strategy for supporting crotamine on gold nanoparticles (GNPs). Our approach was based on the covalent binding interaction between the cell penetrating peptide crotamine, which is a snake venom polypeptide with preference to penetrate dividing cells, and a polyethylene glycol (PEG) ligand, which is a nontoxic, water-soluble and easily obtainable commercial polymer. Crotamine was derivatized with ortho-pyridyldisulfide-polyethyleneglycol-N-hydroxysuccinimide (OPSS-PEG-SVA) cross-linker to produce OPSS-PEG-crotamine as the surface modifier of GNP. OPSS-PEG-SVA can serve not only as a surface modifier, but also as a stabilizing agent for GNPs. The successful PEGylation of the nanoparticles was demonstrated using different physicochemical techniques, while the grafting densities of the PEG ligands and crotamine on the surface of the nanoparticles were estimated using a combination of electron microscopy and mass spectrometry analysis. In vitro assays confirmed the internalization of these GNPs, into living HeLa cells. The results described herein suggest that our approach may serve as a simple platform for the synthesis of GNPs decorated with crotamine with well-defined morphologies and uniform dispersion, opening new roads for crotamine biomedical applications.

Dramatic Modification of Coupled-Plasmon Resonances Following Exposure to Electron Beams.

Studies of the plasmon resonances in individual and coupled metal nanoparticles often involve imaging of the nanostructures of interest in an electron microscope. We show that this process can dramatically modify the optical spectra of coupled plasmonic nanoparticles, illustrated here with the case of gold nanorod-nanosphere dimers. The spectral changes are due to the thin, partially conductive carbonaceous layer that deposits onto the particles during imaging. These changes are particularly significant for coupled nanoparticles with subnanometer interparticle gaps but have largely been neglected in previous studies of such structures, including studies intended to probe quantum-mechanical effects in plasmon coupling. Accounting for the effects of the carbonaceous layer will lead to a more accurate understanding of such systems.