The redistributive effect of the public health system: the case of Sierra Leone.

Universal health coverage (UHC), health equity and reduction of income inequalities are key objectives for the Sierra Leone government. While investing in health systems may drive economic growth, it is less clear whether investing in health systems reduces income inequality. Therefore, a crucial issue is to what extent the Sierra Leone public healthcare system reduces income inequality, and finances and provides healthcare services equitably. We use data from the Sierra Leone Integrated Household Survey 2018 to complete a financing and benefit incidence analysis of the Sierra Leone public healthcare system. We extend these analyses by assessing the redistributive effect of the public healthcare system (i.e. fiscal incidence analysis). We compute the redistributive effect as the change in Gini index induced by the payments for, and provision of, public healthcare services. The financing incidence of the Sierra Leone public healthcare system is marginally progressive (i.e. Kakwani index: 0.011*, P-value <0.1). With regard to public healthcare benefits, while primary healthcare (PHC) benefits are pro-poor, secondary/tertiary benefits are pro-rich. The result is that overall public healthcare benefits are equally distributed (concentration index (CI): 0.008, not statistically different from zero). However, needs are concentrated among the poor, so benefits are pro-rich when needs are considered. We find that the public healthcare system redistributes resources from better-off quintiles to worse-off quintiles (Gini coefficient reduction induced by public healthcare system = 0.5%). PHC receives less financing than secondary/tertiary care but delivers a larger reduction in income inequality. The Sierra Leone public healthcare system redistributes resources and reduces income inequality. However, the redistributive effect occurs largely thanks to PHC services being markedly pro-poor, and the Sierra Leone health system could be more equitable. Policy-makers interested in improving Sierra Leone public health system equity and reducing income inequalities should prioritize PHC investments.

Pharmacological restoration of anti-nociceptive functions in the prefrontal cortex relieves chronic pain.

Chronic pain affects one in four adults, and effective non-sedating and non-addictive treatments are urgently needed. Chronic pain causes maladaptive changes in the cerebral cortex, which can lead to impaired endogenous nociceptive processing. However, it is not yet clear if drugs that restore endogenous cortical regulation could provide an effective therapeutic strategy for chronic pain. Here, we studied the nociceptive response of neurons in the prelimbic region of the prefrontal cortex (PL-PFC) in freely behaving rats using a spared nerve injury (SNI) model of chronic pain, and the impact of AMPAkines, a class of drugs that increase central glutamate signaling, on such response. We found that neurons in the PL-PFC increase their firing rates in response to noxious stimulations; chronic neuropathic pain, however, suppressed this important cortical pain response. Meanwhile, CX546, a well-known AMPAkine, restored the anti-nociceptive response of PL-PFC neurons in the chronic pain condition. In addition, both systemic administration and direct delivery of CX546 into the PL-PFC inhibited symptoms of chronic pain, whereas optogenetic inactivation of the PFC neurons or administration of AMPA receptor antagonists in the PL-PFC blocked the anti-nociceptive effects of CX546. These results indicate that restoration of the endogenous anti-nociceptive functions in the PL-PFC by pharmacological agents such as AMPAkines constitutes a successful strategy to treat chronic neuropathic pain.

HNO to NO Conversion Mechanism with Copper Zinc Superoxide Dismutase, Comparison with Heme Protein Mediated Conversions, and the Origin of Questionable Reversibility.

The interconversion of NO and HNO, via copper zinc superoxide dismutase (CuZnSOD), is important in biomedicine and for HNO detection. Many mechanistic questions, including the decades-long debate on reversibility, were resolved in this work. Calculations of various active-site and full-protein models show that the basic mechanism is proton-coupled electron transfer with a computed barrier of 10.98 kcal mol-1 , which is in excellent agreement with experimental results (10.62 kcal mol-1 ), and this nonheme protein-mediated reaction has many significant mechanistic differences compared with the conversions mediated by heme proteins due to geometric and electronic factors. The reasons for the irreversible nature of this conversion and models with the first thermodynamically favorable and kinetically feasible mechanism for the experimental reverse reaction were discovered. Such results are the first for nonheme enzyme mediated HNO to NO conversions, which shall facilitate other related studies and HNO probe development.

An Asymptomatic Patient with COVID-19 with Hip Hemiarthroplasty Performed: A Case Report of an Orthopaedic Surgeon's Experience.

CASE: Coronavirus disease 2019 (COVID-19) is a pandemic respiratory disease. Patients typically present with fever, cough, and radiological lung changes. However, a significant proportion of these patients are asymptomatic. To date, we have limited information on the operations performed on these patients. We report our experience of a relatively asymptomatic elderly patient who underwent surgery for a hip fracture and was confirmed postoperatively to have COVID-19. CONCLUSION: Meticulous hand hygiene and use of surgical mask in daily practice is crucial to protect against asymptomatic and undiagnosed patients.

Denial of Suicide Attempt Among Hospitalized Survivors of a Self-Inflicted Gunshot Wound.

OBJECTIVE: Evidence suggests that suicide attempts by self-inflicted gunshot wound (GSW) are underreported and may in turn affect disposition following hospitalization. This study aimed to evaluate the clinical characteristics and use of services among individuals who do not disclose suicidal intent following a self-inflicted GSW. METHODS: Electronic medical record data from 128 survivors of self-inflicted GSWs at a level 1 trauma center were analyzed to identify factors associated with nondisclosure of a suicide attempt to medical staff. RESULTS: Results indicated that 29% of patients denied that a self-inflicted GSW was a suicide attempt, and 43% of patients who denied suicidal intent were identified by the psychiatric consultation and liaison service as presenting under circumstances suspicious of a suicide attempt. Logistic regression analyses indicated that patients who denied having attempted suicide were 10.86 times more likely to be discharged to home than patients who disclosed suicidal intent. In a multiple regression model, no clinical or demographic characteristics were significantly associated with nondisclosure of suicide intent. CONCLUSIONS: Patients' nondisclosure of suicidal intent following a self-inflicted GSW may present a barrier to care for patients whose injuries are the result of a suicide attempt. Implications for reducing barriers to care for a high-risk population are discussed, including the impact of nondisclosure on future treatment and the potential utility of brief interventions for suicide risk reduction.

Why copper is preferred over iron for oxygen activation and reduction in haem-copper oxidases.

Haem-copper oxidase (HCO) catalyses the natural reduction of oxygen to water using a haem-copper centre. Despite decades of research on HCOs, the role of non-haem metal and the reason for nature's choice of copper over other metals such as iron remains unclear. Here, we use a biosynthetic model of HCO in myoglobin that selectively binds different non-haem metals to demonstrate 30-fold and 11-fold enhancements in the oxidase activity of Cu- and Fe-bound HCO mimics, respectively, as compared with Zn-bound mimics. Detailed electrochemical, kinetic and vibrational spectroscopic studies, in tandem with theoretical density functional theory calculations, demonstrate that the non-haem metal not only donates electrons to oxygen but also activates it for efficient O-O bond cleavage. Furthermore, the higher redox potential of copper and the enhanced weakening of the O-O bond from the higher electron density in the d orbital of copper are central to its higher oxidase activity over iron. This work resolves a long-standing question in bioenergetics, and renders a chemical-biological basis for the design of future oxygen-reduction catalysts.

Functional neuroanatomical correlates of episodic memory impairment in early phase psychosis.

Studies have demonstrated that episodic memory (EM) is often preferentially disrupted in schizophrenia. The neural substrates that mediate EM impairment in this illness are not fully understood. Several functional magnetic resonance imaging (fMRI) studies have employed EM probe tasks to elucidate the neural underpinnings of impairment, though results have been inconsistent. The majority of EM imaging studies have been conducted in chronic forms of schizophrenia with relatively few studies in early phase patients. Early phase schizophrenia studies are important because they may provide information regarding when EM deficits occur and address potential confounds more frequently observed in chronic populations. In this study, we assessed brain activation during the performance of visual scene encoding and recognition fMRI tasks in patients with earlyphase psychosis (n = 35) and age, sex, and race matched healthy control subjects (n = 20). Patients demonstrated significantly lower activation than controls in the right hippocampus and left fusiform gyrus during scene encoding and lower activation in the posterior cingulate, precuneus, and left middle temporal cortex during recognition of target scenes. Symptom levels were not related to the imaging findings, though better cognitive performance in patients was associated with greater right hippocampal activation during encoding. These results provide evidence of altered function in neuroanatomical circuitry subserving EM early in the course of psychotic illness, which may have implications for pathophysiological models of this illness.

Toward Relatively General and Accurate Quantum Chemical Predictions of Solid-State (17)O NMR Chemical Shifts in Various Biologically Relevant Oxygen-Containing Compounds.

Oxygen is an important element in most biologically significant molecules, and experimental solid-state (17)O NMR studies have provided numerous useful structural probes to study these systems. However, computational predictions of solid-state (17)O NMR chemical shift tensor properties are still challenging in many cases, and in particular, each of the prior computational works is basically limited to one type of oxygen-containing system. This work provides the first systematic study of the effects of geometry refinement, method, and basis sets for metal and nonmetal elements in both geometry optimization and NMR property calculations of some biologically relevant oxygen-containing compounds with a good variety of XO bonding groups (X = H, C, N, P, and metal). The experimental range studied is of 1455 ppm, a major part of the reported (17)O NMR chemical shifts in organic and organometallic compounds. A number of computational factors toward relatively general and accurate predictions of (17)O NMR chemical shifts were studied to provide helpful and detailed suggestions for future work. For the studied kinds of oxygen-containing compounds, the best computational approach results in a theory-versus-experiment correlation coefficient (R(2)) value of 0.9880 and a mean absolute deviation of 13 ppm (1.9% of the experimental range) for isotropic NMR shifts and an R(2) value of 0.9926 for all shift-tensor properties. These results shall facilitate future computational studies of (17)O NMR chemical shifts in many biologically relevant systems, and the high accuracy may also help the refinement and determination of active-site structures of some oxygen-containing substrate-bound proteins.

HNO/NO Conversion Mechanisms of Cu-Based HNO Probes with Implications for Cu,Zn-SOD.

HNO has broad biological effects and pharmacological activities. Direct HNO probes for in vivo applications were recently reported, which are CuII-based complexes having fluorescence reporters with reaction to HNO resulting in CuI systems and the release of NO. Their coordination environments are similar to that in Cu,Zn-superoxide dismutase (SOD), which plays a significant role in cellular HNO/NO conversion. However, none of these conversion mechanisms are known. A quantum chemical investigation was performed here to provide structural, energetic, and electronic profiles of HNO/NO conversion pathways via the first CuII-based direct HNO probe. Results not only are consistent with experimental observations but also provide numerous structural and mechanistic details unknown before. Results also suggest the first HNO/NO conversion mechanism for Cu,Zn-SOD, as well as useful guidelines for future design of metal-based HNO probes. These results shall facilitate development of direct HNO probes and studies of HNO/NO conversions via metal complexes and metalloproteins.

The single-stranded DNA-binding protein of Deinococcus radiodurans.

BACKGROUND: Deinococcus radiodurans R1 is one of the most radiation-resistant organisms known and is able to repair an unusually large amount of DNA damage without induced mutation. Single-stranded DNA-binding (SSB) protein is an essential protein in all organisms and is involved in DNA replication, recombination and repair. The published genomic sequence from Deinococcus radiodurans includes a putative single-stranded DNA-binding protein gene (ssb; DR0100) requiring a translational frameshift for synthesis of a complete SSB protein. The apparently tripartite gene has inspired considerable speculation in the literature about potentially novel frameshifting or RNA editing mechanisms. Immediately upstream of the ssb gene is another gene (DR0099) given an ssb-like annotation, but left unexplored. RESULTS: A segment of the Deinococcus radiodurans strain R1 genome encompassing the ssb gene has been re-sequenced, and two errors involving omitted guanine nucleotides have been documented. The corrected sequence incorporates both of the open reading frames designated DR0099 and DR0100 into one contiguous ssb open reading frame (ORF). The corrected gene requires no translational frameshifts and contains two predicted oligonucleotide/oligosaccharide-binding (OB) folds. The protein has been purified and its sequence is closely related to the Thermus thermophilus and Thermus aquaticus SSB proteins. Like the Thermus SSB proteins, the SSBDr functions as a homodimer. The Deinococcus radiodurans SSB homodimer stimulates Deinococcus radiodurans RecA protein and Escherichia coli RecA protein-promoted DNA three-strand exchange reactions with at least the same efficiency as the Escherichia coli SSB homotetramer. CONCLUSIONS: The correct Deinococcus radiodurans ssb gene is a contiguous open reading frame that codes for the largest bacterial SSB monomer identified to date. The Deinococcus radiodurans SSB protein includes two OB folds per monomer and functions as a homodimer. The Deinococcus radiodurans SSB protein efficiently stimulates Deinococcus radiodurans RecA and also Escherichia coli RecA protein-promoted DNA strand exchange reactions. The identification and purification of Deinococcus radiodurans SSB protein not only allows for greater understanding of the SSB protein family but provides an essential yet previously missing player in the current efforts to understand the extraordinary DNA repair capacity of Deinococcus radiodurans.