Exploring the Role of External Beam Radiation Therapy in Osteosarcoma Treatment: Impact of Diagnostic Imaging Delays and Innovative Techniques.

Osteosarcomas are a type of bone cancer that typically affect young adults, often in the bones of the arms and legs. To treat osteosarcoma, doctors typically use a combination of chemotherapy, radiotherapy, and surgery, with External Beam Radiation Therapy (EBRT) being the most commonly used form of radiotherapy. EBRT involves directing high-energy photons, X-rays, gamma rays, protons, and electrons at the tumor to induce cancer cell death. Additionally, healthcare providers use imaging techniques to monitor treatment success. This literature review aims to explore the relationship between osteosarcomas and EBRT, investigate the impact of the delayed diagnosis on survival rates, and examine the effectiveness of innovative uses of EBRT for treating osteosarcomas in unusual locations using comprehensive diagnostic techniques. To achieve these objectives, the review examines case studies and literary analyses and categorizes them based on the delay between symptom onset and diagnosis. The null hypothesis is that the presence or absence of a delay in diagnosis does not significantly impact outcomes for the "Delay" category. A lack of delay results in a more favorable outcome in the "Lack of Delay" category. However, the data and statistical results suggest that additional follow-up care in patients with rare or commonly recurring cancers could benefit outcomes. It is important to note that due to the rarity of osteosarcoma with EBRT, the small sample size in the studies warrants further investigation. Interestingly, many patients presented with head and neck tumors despite the most common location of osteosarcoma being in the long bones.

An Investigation on the Efficacy of Glucagon-Like Peptide 1 Receptor Agonists Drugs in Reducing Urine Albumin-to-Creatinine Ratio in Patients With Type 2 Diabetes: A Potential Treatment for Diabetic Nephropathy.

As diabetes mellitus becomes increasingly prevalent globally, so does diabetic nephropathy, a complication leading to one of the world's leading causes of end-stage renal disease (ESRD). Current research has linked an increase in the urine albumin-to-creatinine ratio (UACR), a marker for kidney damage, to a greater risk of adverse renal outcomes and ESRD in patients with diabetes. Of the diabetes medications studied and implemented in clinical settings, glucagon-like peptide-1 receptor agonist (GLP1-RA) drugs have been shown to not only help control HbA1c in diabetes but have also demonstrated numerous cardiovascular, hepatic, and renal benefits. The objective of our study was to assess the efficacy of GLP1-RA drugs in reducing UACR in patients with type 2 diabetes mellitus (T2 DM) to determine if GLP1-RAs could be used to provide renoprotection in diabetic nephropathy in addition to their glucose-lowering effects. Upon a comprehensive review of the literature, we conducted a statistical analysis to determine the efficacy of GLP1-RA monotherapy and combination therapy in reducing UACR in comparison to placebo and insulin glargine. Of the studies analyzed, GLP1-RAs exhibited a statistically significant effect in reducing UACR in comparison to a placebo but not in comparison to insulin glargine. GLP1-RA combination therapy (GLP1-RA used with either insulin glargine, metformin, or dapagliflozin) did not exhibit statistically significant UACR reductions in comparison with insulin glargine. However, GLP1-RA combination therapy showed a trend suggestive of being more effective than insulin glargine in reducing UACR, but due to the limited literature studying this treatment method, further studies in a more focused group of patients with diabetic nephropathy may produce stronger and more definitive results. GLP1-RA monotherapy or combination therapy has been determined to be an effective method for reducing UACR and decreasing the incidence of adverse renal outcomes associated with diabetic kidney disease. GLP1-RA therapy could serve as an alternative treatment in diabetic nephropathy to insulin glargine, which carries a higher risk of hypoglycemia and unintentional weight gain while potentially being less cost-effective.

Changes in Resting-State Neural Activity and Nerve Fibres in Ischaemic Stroke Patients with Hemiplegia.

Many neuroimaging studies have reported that stroke induces abnormal brain activity. However, little is known about resting-state networks (RSNs) and the corresponding white matter changes in stroke patients with hemiplegia. Here, we utilized functional magnetic resonance imaging (fMRI) to measure neural activity and related fibre tracts in 14 ischaemic stroke patients with hemiplegia and 12 healthy controls. Fractional amplitude of low-frequency fluctuations (fALFF) calculation and correlation analyses were used to assess the relationship between regional neural activity and movement scores. Tractography was performed using diffusion tensor imaging (DTI) data to analyse the fibres passing through the regions of interest. Compared with controls, stroke patients showed abnormal functional connectivity (FC) between some brain regions in the RSNs. The fALFF was increased in the contralesional parietal lobe, with the regional fALFF being correlated with behavioural scores in stroke patients. Additionally, the passage of fibres across regions with reduced FC in the RSNs was increased in stroke patients. This study suggests that structural remodelling of functionally relevant white matter tracts is probably an adaptive response that compensates for injury to the brain.

An Exploration of the Unintended Consequences of Performance-Based Financing in 6 Primary Healthcare Facilities in Burkina Faso.

BACKGROUND: Performance-based financing (PBF) is promoted to improve the quality and quantity of healthcare services in low-income countries. Despite the complexity of the intervention, little attention has been given to studying its unintended consequences. Our objective is to increase evidence on the unintended consequences of PBF in Burkina Faso. METHODS: Using the diffusion of innovations theory, we conducted a multiple case study. The cases were 6 healthcare facilities in two districts. Between April 2015 and 2016, we collected data through 101 semi-structured interviews, discussions, observations, and documents. We conducted thematic analysis using a hybrid deductive-inductive approach. Secondary data was used to illustrate the evolution of reported services. We conducted a cross-case synthesis to identify the results arising independently from more than 1 case. RESULTS: A desirable unintended consequence of PBF was that 3 facilities limited the sale of non-prescribed medication to encourage patients to consult. Undesirable unintended consequences were found in the majority of facilities including fixation on measures rather than on underlying objectives, the pursuit of narrow and less relevant performance indicators, gaming, and teaching trainees improper practices. Providers in all facilities deliberately manipulated medical registers and documents, such that the reported quantity and quality of care differed from what was actually delivered. While most participants indicated that PBF was more advantageous than previous practices, the long payment delays were a source of dissatisfaction and demotivation across all facilities. Dissatisfaction also emerged in relation to the distribution of subsidies and the non-attribution of quality points for services delivered by certain staff considered "unqualified" in guidelines. Results in many facilities revealed suboptimal planning, a perception of the intervention as "budgetivorous," as well as tensions related to the principle of managerial autonomy. CONCLUSION: PBF led to numerous unintended consequences that could undermine the intervention's effectiveness. The findings contribute to a more comprehensive picture of the consequences of implementing PBF. Policy-makers can use the results of this study to devise effective strategies before, during and after the implementation of the intervention to minimize undesirable unintended consequences and promote desirable ones.

N-Butylphthalide vs. Human Urinary Kallidinogenase for the Treatment of Acute Ischemic Stroke: Functional Outcome and Impact on Serum VEGF and TNF-α Expressions.

OBJECTIVE: To compare the e!cacy and functional outcomes of dl-3-n-Butylphthalide (NBP) and human urinary kallidinogenase (HUK) on ischemic stroke patients and to determine their effects on serum tumor necrosis factor-alpha (TNF-α) and vascular endothelial growth factor (VEGF). METHODS: A prospective study was conducted on 57 ischemic stroke patients. Functional outcomes were assessed by the National Institute Health Stroke Scale (NIHSS), the modified Rankin Scale (mRS), and the activities of daily living score (ADL), whereas TNF-α and VEGF expressions were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: TNF-α was significantly down-regulated in the NBP group and upregulated in the control group two weeks after treatment (p=0.017 and p=0.047, respectively). A significant difference in VEGF expressions was observed between the two groups (330.25±120.64 vs. 437.15±137.68, p=0.041) two weeks after treatment. Both groups showed significant improvement in NIHSS and ADL scores three months after treatment (p<0.001), with the NBP group exhibiting improvement in NIHSS scores as early as two weeks after treatment (p=0.008). The three-month NIHSS scores of the two groups were significantly lower than those of the control group (p=0.010 and p=0.008, respectively). Both the NBP and HUK groups showed a significant decline in mRS scores two weeks and three months after treatment (p<0.05). CONCLUSIONS: Both treatments are effective and can significantly promote recovery in stroke patients. Additionally, both options have similar effects in promoting long-term recovery, with NBP exerting a greater impact on serum VEGF and TNF-α expressions.

White matter degeneration in remote brain areas of stroke patients with motor impairment due to basal ganglia lesions.

Diffusion tensor imaging (DTI) studies have revealed distinct white matter (WM) characteristics of the brain following diseases. Beyond the lesion-symptom maps, stroke is characterized by extensive structural and functional alterations of brain areas remote to local lesions. Here, we further investigated the structural changes over a global level by using DTI data of 10 ischemic stroke patients showing motor impairment due to basal ganglia lesions and 11 healthy controls. DTI data were processed to obtain fractional anisotropy (FA) maps, and multivariate pattern analysis was used to explore brain regions that play an important role in classification based on FA maps. The WM structural network was constructed by the deterministic fiber-tracking approach. In comparison with the controls, the stroke patients showed FA reductions in the perilesional basal ganglia, brainstem, and bilateral frontal lobes. Using network-based statistics, we found a significant reduction in the WM subnetwork in stroke patients. We identified the patterns of WM degeneration affecting brain areas remote to the lesions, revealing the abnormal organization of the structural network in stroke patients, which may be helpful in understanding of the neural mechanisms underlying hemiplegia.

Ketamine Induces Lasting Antidepressant Effects by Modulating the NMDAR/CaMKII-Mediated Synaptic Plasticity of the Hippocampal Dentate Gyrus in Depressive Stroke Model.

Background: Ketamine has been shown to possess lasting antidepressant properties. However, studies of the mechanisms involved in its effects on poststroke depression are nonexistent. Methods: To investigate these mechanisms, Sprague-Dawley rats were treated with a single local dose of ketamine after middle cerebral artery occlusion and chronic unpredicted mild stress. The effects on the hippocampal dentate gyrus were analyzed through assessment of the N-methyl-D-aspartate receptor/calcium/calmodulin-dependent protein kinase II (NMDAR/CaMKII) pathway, synaptic plasticity, and behavioral tests. Results: Ketamine administration rapidly exerted significant and lasting improvements of depressive symptoms. The biochemical analysis showed rapid, selective upregulation and downregulation of the NMDAR2-ß and NMDAR2-α subtypes as well as their downstream signaling proteins ß-CaMKII and α-phosphorylation in the dentate gyrus, respectively. Furthermore, the colocalization analysis indicated a significant and selectively increased conjunction of ß-CaMKII and postsynaptic density protein 95 (PSD95) coupled with a notable decrease in NMDAR2-ß association with PSD95 after ketamine treatment. These changes translated into significant and extended synaptic plasticity in the dentate gyrus. Conclusions: These findings not only suggest that ketamine represents a viable candidate for the treatment of poststroke depression but also that ketamine's lasting antidepressant effects might be achieved through modulation of NMDAR/CaMKII-induced synaptic plasticity in key brain regions.

A novel recessive mutation affecting DNAJB6a causes myofibrillar myopathy.

Mutations in the DNAJB6 gene have been identified as rare causes of myofibrillar myopathies. However, the underlying pathophysiologica mechanisms remain elusive. DNAJB6 has two known isoforms, including the nuclear isoform DNAJB6a and the cytoplasmic isoform DNAJB6b, which was thought to be the pathogenic isoform. Here, we report a novel recessive mutation c.695_699del (p. Val 232 Gly fs*7) in the DNAJB6 gene, associated with an apparently recessively inherited late onset distal myofibrillar myopathy in a Chinese family. Notably, the novel mutation localizes to exon 9 and uniquely encodes DNAJB6a. We further identified that this mutation decreases the mRNA and protein levels of DNAJB6a and results in an age-dependent recessive toxic effect on skeletal muscle in knock-in mice. Moreover, the mutant DNAJB6a showed a dose-dependent anti-aggregation effect on polyglutamine-containing proteins in vitro. Taking together, these findings reveal the pathogenic role of DNAJB6a insufficiency in myofibrillar myopathies and expand upon the molecular spectrum of DNAJB6 mutations.

The unintended consequences of COVID-19 mitigation measures matter: practical guidance for investigating them.

BACKGROUND: COVID-19 has led to the adoption of unprecedented mitigation measures which could trigger many unintended consequences. These unintended consequences can be far-reaching and just as important as the intended ones. The World Health Organization identified the assessment of unintended consequences of COVID-19 mitigation measures as a top priority. Thus far, however, their systematic assessment has been neglected due to the inattention of researchers as well as the lack of training and practical tools. MAIN TEXT: Over six years our team has gained extensive experience conducting research on the unintended consequences of complex health interventions. Through a reflexive process, we developed insights that can be useful for researchers in this area. Our analysis is based on key literature and lessons learned reflexively in conducting multi-site and multi-method studies on unintended consequences. Here we present practical guidance for researchers wishing to assess the unintended consequences of COVID-19 mitigation measures. To ensure resource allocation, protocols should include research questions regarding unintended consequences at the outset. Social science theories and frameworks are available to help assess unintended consequences. To determine which changes are unintended, researchers must first understand the intervention theory. To facilitate data collection, researchers can begin by forecasting potential unintended consequences through literature reviews and discussions with stakeholders. Including desirable and neutral unintended consequences in the scope of study can help minimize the negative bias reported in the literature. Exploratory methods can be powerful tools to capture data on the unintended consequences that were unforeseen by researchers. We recommend researchers cast a wide net by inquiring about different aspects of the mitigation measures. Some unintended consequences may only be observable in subsequent years, so longitudinal approaches may be useful. An equity lens is necessary to assess how mitigation measures may unintentionally increase disparities. Finally, stakeholders can help validate the classification of consequences as intended or unintended. CONCLUSION: Studying the unintended consequences of COVID-19 mitigation measures is not only possible but also necessary to assess their overall value. The practical guidance presented will help program planners and evaluators gain a more comprehensive understanding of unintended consequences to refine mitigation measures.

Melatonin Ameliorates Lipopolysaccharide-Induced Microglial Inflammation via Triggering SIRT1/HMGB1 Signaling Axis.

Stroke is one of the highest incidence neurological disorder with great morbidity and mortality rate. The secondary neuroinflammation contributed by microglial activation is a consequential response observed in the pathogenesis of stroke. High-mobility group box 1, a non-histone nuclear protein, interacts with immune cells, such as microglia, and leads to a cascade amplification of the secondary neuroinflammatory responses, which are related to neuronal damage later. Melatonin is a neurohormone, well-known as its anti-oxidative and anti-inflammatory effects. However, until now, more findings are required for better understanding about anti-inflammatory effect of melatonin on HMGB1 and HMGB1-triggered pathway in LPS-induced microglial activation. Melatonin effect on the viability of BV2 microglial cells was measured by CCK-8 assay; mRNA levels of HMGB1 and other inflammatory cytokines were determined by quantitative real-time polymerase chain reaction assay or enzyme-linked immunosorbent assays; the protein expression levels of TLR4/MyD88/NF-κB and SIRT1 were detected by Western blot, and HMGB1 translocation and release from BV2 microglial cells were examined by immunofluorescence assay. The results of this study demonstrated that melatonin suppressed LPS-triggered BV2 microglial activation-mediated inflammation by inhibiting high expression and release of HMGB1 and moderating the activation of subsequent TLR4/MyD88/NF-κB signaling pathway, which was activated by SIRT1 elevation. Furthermore, LPS-induced expression of pro-inflammatory cytokines (i.e., TNF-α, IL-6, and IL-1ß) was notably reversed by melatonin pre-treatment. In summary, our findings suggest that melatonin may act as a promising therapeutic agent for reducing post-stroke neuroinflammation by targeting HMGB1 and the subsequent signaling axis.

Long-term immunogenicity and immune memory response to the hepatitis B antigen in the RTS,S/AS01E malaria vaccine in African children: a randomized trial.

RTS,S/AS01E malaria vaccine contains the hepatitis B virus surface antigen and may thus serve as a potential hepatitis B vaccine. To evaluate the impact of RTS,S/AS01E when implemented in the Expanded Program of Immunization, infants 8-12 weeks old were randomized to receive either RTS,S/AS01E or a licensed hepatitis B control vaccine (HepB), both co-administered with various combinations of the following childhood vaccines: diphtheria-tetanus-acellular pertussis-Haemophilus influenzae type b, trivalent oral poliovirus, pneumococcal non-typeable Haemophilus influenzae protein D conjugate and human rotavirus vaccine. Long-term persistence of antibodies against the circumsporozoite (CS) protein and hepatitis B surface antigen (HBsAg) were assessed, together with the immune memory response to the HB antigen following a booster dose of HepB vaccine. Subgroups receiving RTS,S or the HepB control vaccine were pooled into RTS,S groups and HepB groups, respectively. One month post-HepB booster vaccination, 100% of participants in the RTS,S groups and 98.3% in the control groups had anti-HBs antibody concentrations ≥10 mIU/mL with the geometric mean concentrations (GMCs) at 46634.7 mIU/mL (95% CI: 40561.3; 53617.6) and 9258.2 mIU/mL (95% CI: 6925.3; 12377.0), respectively. Forty-eight months post-primary vaccination anti-CS antibody GMCs ranged from 2.3 EU/mL to 2.7 EU/mL in the RTS,S groups compared to 1.1 EU/mL in the control groups. Hepatitis B priming with the RTS,S/AS01E vaccine was effective and resulted in a memory response to HBsAg as shown by the robust booster response following an additional dose of HepB vaccine. RTS,S/AS01E when co-administered with PHiD-CV, HRV and other childhood vaccines, had an acceptable safety profile.

The unintended consequences of combining equity measures with performance-based financing in Burkina Faso.

BACKGROUND: User fees and poor quality of care contribute to low use of healthcare services in Burkina Faso. The government implemented an innovative intervention that combines equity measures with performance-based financing (PBF). These health equity measures included a community-based selection of indigents to receive user fee exemptions and paying healthcare centres higher purchase prices for services provided to indigents. Research suggests complex interventions can trigger changes not targeted by program planners. To date, however, there is a knowledge gap regarding the unintended consequences that can emerge from combining PBF with health equity measures. Our objective is to document unintended consequences of the equity measures in this complex intervention. METHODS: We developed a conceptual framework using the diffusion of innovations theory. For the design, we conducted a multiple case study. The cases were four healthcare facilities in one district. We collected data through 93 semi-structured interviews, informal discussions, observation, as well as intervention documents. We conducted thematic analysis using a hybrid deductive-inductive approach. We also used secondary data to describe the monthly evolution of services provided to indigent and non-indigent patients before and after indigent cards were distributed. Time series graphs were used to validate some results. RESULTS: Local actors, including members of indigent selection committees and healthcare workers, re-invented elements of the PBF equity measures over which they had control to increase their relative advantage or to adapt to implementation challenges and context. Some individuals who did not meet the local conceptualization of indigents were selected to the detriment of others who did. Healthcare providers believed that distributing free medications led to financial difficulties and drug shortages, especially given the low purchase prices and long payment delays. Healthcare workers adopted measures to limit free services delivered to indigents, which led to conflicts between indigents and providers. Ultimately, selected indigents received uncertain and unequal coverage. CONCLUSIONS: The severity of unintended consequences undermined the effectiveness and equity of the intervention. If the intervention is prolonged and expanded, decision-makers and implementers will have to address these unintended consequences to reduce inequities in accessing care.

Association of circulating blood HMGB1 levels with ischemic stroke: a systematic review and meta-analysis.

OBJECTIVES: Inflammation plays a key role in the pathogenesis and progression of ischemic stroke (IS). The high mobility group box 1 (HMGB1) nucleoprotein is involved in the amplification of inflammatory responses during acute ischemic injury. HMGB1 levels in patients with active disease are higher than those in healthy controls. We performed a meta-analysis to assess currently published data pertaining to circulating blood HMGB1 levels in IS and the relationship with stroke severity. METHODS: We systematically searched for studies investigating the circulating blood HMGB1 levels in patients with IS in PubMed/Medline, Embase, the Cochrane Library, Web of science and China National Knowledge Infrastructure (CNKI). Two independent researchers used the Cochrane Collaboration tools for data extraction and quality assessment. Extracted data were analyzed by Review Manager version 5.3. RESULTS: A total of 28 studies were included with a total of 4497 participants, including 2671 IS patients and 1826 matched controls. The meta-analysis revealed that compared with control, IS patients had higher circulating blood HMGB1 levels (n = 4497, standardized mean difference (SMD) = 5.70, 95%confidence interval (CI) = 4.79 to 6.62, Z = 12.23, P < 0.00001), and the HMGB1 level was positively correlated with severity (n = 507, SMD = -2.12, 95%CI = -3.41 to -0.82, Z = 3.20, P < 0.00001) and infarct volume (n = 582, 95%CI = -4.06 to -1.70, Z = 4.79, P < 0.00001). CONCLUSIONS: This meta-analysis demonstrates that circulating blood HMGB1 levels elevate in IS and higher HMGB1 levels may indicate a more serious condition.

Immune response to the hepatitis B antigen in the RTS,S/AS01 malaria vaccine, and co-administration with pneumococcal conjugate and rotavirus vaccines in African children: A randomized controlled trial.

The RTS,S/AS01 malaria vaccine (Mosquirix) reduces the incidence of Plasmodium falciparum malaria and is intended for routine administration to infants in Sub-Saharan Africa. We evaluated the immunogenicity and safety of 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV; Synflorix) and human rotavirus vaccine (HRV; Rotarix) when co-administered with RTS,S/AS01 ( www.clinicaltrials.gov NCT01345240) in African infants. 705 healthy infants aged 8-12 weeks were randomized to receive three doses of either RTS,S/AS01 or licensed hepatitis B (HBV; Engerix B) vaccine (control) co-administered with diphtheria-tetanus-acellular pertussis-Haemophilus influenzae type-b-conjugate vaccine (DTaP/Hib) and trivalent oral poliovirus vaccine at 8-12-16 weeks of age, because DTaP/Hib was not indicated before 8 weeks of age. The vaccination schedule can still be considered broadly applicable because it was within the age range recommended for EPI vaccination. PHiD-CV or HRV were either administered together with the study vaccines, or after a 2-week interval. Booster doses of PHiD-CV and DTaP/Hib were administered at age 18 months. Non-inferiority of anti-HBV surface antigen antibody seroprotection rates following co-administration with RTS,S/AS01 was demonstrated compared to the control group (primary objective). Pre-specified non-inferiority criteria were reached for PHiD-CV (for 9/10 vaccine serotypes), HRV, and aP antigens co-administered with RTS,S/AS01 as compared to HBV co-administration (secondary objectives). RTS,S/AS01 induced a response to circumsporozoite protein in all groups. Pain and low grade fever were reported more frequently in the PHiD-CV group co-administered with RTS,S/AS01 than PHiD-CV co-administered with HBV. No serious adverse events were considered to be vaccine-related. RTS,S/AS01 co-administered with pediatric vaccines had an acceptable safety profile. Immune responses to RTS,S/AS01 and to co-administered PHiD-CV, pertussis antigens and HRV were satisfactory.

The unintended consequences of community verifications for performance-based financing in Burkina Faso.

Performance-based financing (PBF) is being widely implemented to improve healthcare services in Africa. An essential component of PBF involves conducting community verifications, wherein investigators from local associations attempt to trace samples of patients. Community surveys are administered to patients to verify whether healthcare workers reported fictitious services to increase their revenue. At the same time, client satisfaction surveys are administered to assess whether patients are satisfied with the services received. Although some global health actors are concerned that PBF can trigger unintended consequences, this topic remains neglected. The objective of this study was to document the unintended consequences of community verification. Guided by the diffusion of innovations theory, we conducted a multiple case study. The cases were the catchment areas of seven healthcare facilities in Burkina Faso. Data were collected between January 2016 and May 2016 using non-participant observation, 92 semi-structured interviews, and informal discussions. Participants included a wide range of stakeholders, such as community verifiers, investigators, patients, and healthcare providers. Data were coded using QDA Miner, and thematic analysis was conducted. Healthcare workers did not significantly disturb or try to influence community verifiers during patient selection for community verifications. Unintended consequences included stakeholders' dissatisfaction regarding compensation modalities, work overload for community verifiers, and falsification of verification data by investigators. Community verifications led to loss of patient confidentiality as well as fears and apprehensions, although some patients were pleased to share their views regarding healthcare services. Community verifications also triggered marital issues, resulting in conflicts with, or interference from, husbands. The numerous challenges associated with locating patients in their communities led stakeholders to question the validity and utility of the results. These unintended consequences could jeopardize the overall effectiveness of community verifications. Attention should be paid to these unintended consequences to inform effective implementation and refine future interventions.

A Review of Recent Advances in Neuroprotective Potential of 3-N-Butylphthalide and Its Derivatives.

The research of alternative treatment for ischemic stroke and degenerative diseases has always been a priority in neurology. 3-N-Butylphthalide (NBP), a family of compounds initially isolated from the seeds of Apium graveolens Linn., has shown significant neuroprotective effects. Previous extensive studies have demonstrated that NBP promotes a better poststroke outcome and exerts a multitargeted action on several mechanisms, from oxidative stress to mitochondrial dysfunction to apoptosis to inflammation. Additionally, recent findings on several neurological disorders have shown that NBP's beneficial effects extend beyond the management of stroke. However, despite the increasing number of studies toward a better understanding and the rapid advances made in therapeutic options, to date, dl-3-N-butylphthalide, a synthetic variation of l-3-N-butylphthalide, remains the only clinically approved anti-ischemic agent in China, stressing the difficulties for a viable and effective transition from experimental to clinical practice. Events indicate that NBP, due to its multitargeted effect and the adaptability of its basic structure, can be an important game changer and a precursor to a whole new therapeutic approach to several neurological conditions. The present review discusses recent advances pertaining to the neuroprotective mechanisms of NBP-derived compounds and the possibility of their clinical implementation in the management of various neurological conditions.

Gastrointestinal and urinary tract pathogenic infections among HIV seropositive patients at the Komfo Anokye Teaching Hospital in Ghana.

BACKGROUND: Gastrointestinal and urinary tract pathogenic infections are aggravating the incidence and progression of the Human Immunodeficiency Virus (HIV) infection into Acquired Immune Deficiency Syndrome (AIDS) more especially in the developing countries. This study was conducted to assess the common gastrointestinal and urinary infections among HIV/AIDS patients at the Komfo Anokye Teaching Hospital (KATH) in Ghana between April and December 2008. FINDINGS: This work reports on gastrointestinal and urinary tract pathogenic infections among 500 HIV seropositive and 300 HIV seronegative patients. There was a 35% (175/500) prevalence of intestinal parasites among HIV seropositive patients compared to 4.3% (13/300) in HIV seronegative patients. Giardia lamblia and Cryptosporidium accounted for 19% (95/500) and 14% (70/500) respectively, while Schistosoma mansoni, Strongyloides stercoralis and hookworm together accounted for 2% (10/500) of intestinal parasitic infections among the HIV seropositive patients. There was no significant difference (p > 0.05) in urinary parasitic infection between HIV seropositive 1% (2/500) and seronegative patients 0.7% (2/300). Most, 60 (86%) out of 70, of the urinary tract infection among the HIV seropositive patients was due to bacteria with E. coli being the most predominant isolate, 28 (47%) out of 60. There was no significant difference in infections based on age and gender. CONCLUSION: G. lamblia and Cryptosporidium were the most common gastrointestinal parasites detected while bacteria accounted for majority of the urinary tract infections among the HIV seropositive patients at the hospital.

Hemoglobin estimation by the HemoCue® portable hemoglobin photometer in a resource poor setting.

BACKGROUND: In resource poor settings where automated hematology analyzers are not available, the Cyanmethemoglobin method is often used. This method though cheaper, takes more time. In blood donations, the semi-quantitative gravimetric copper sulfate method which is very easy and inexpensive may be used but does not provide an acceptable degree of accuracy. The HemoCue® hemoglobin photometer has been used for these purposes. This study was conducted to generate data to support or refute its use as a point-of-care device for hemoglobin estimation in mobile blood donations and critical care areas in health facilities. METHOD: EDTA blood was collected from study participants drawn from five groups: pre-school children, school children, pregnant women, non-pregnant women and men. Blood collected was immediately processed to estimate the hemoglobin concentration using three different methods (HemoCue®, Sysmex KX21N and Cyanmethemoglobin). Agreement between the test methods was assessed by the method of Bland and Altman. The Intraclass correlation coefficient (ICC) was used to determine the within subject variability of measured hemoglobin. RESULTS: Of 398 subjects, 42% were males with the overall mean age being 19.4 years. The overall mean hemoglobin as estimated by each method was 10.4 g/dl for HemoCue, 10.3 g/dl for Sysmex KX21N and 10.3 g/dl for Cyanmethemoglobin. Pairwise analysis revealed that the hemoglobin determined by the HemoCue method was higher than that measured by the KX21N and Cyanmethemoglobin. Comparing the hemoglobin determined by the HemoCue to Cyanmethemoglobin, the concordance correlation coefficient was 0.995 (95% CI: 0.994-0.996, p < 0.001). The Bland and Altman's limit of agreement was -0.389 - 0.644 g/dl with the mean difference being 0.127 (95% CI: 0.102-0.153) and a non-significant difference in variability between the two measurements (p = 0.843). After adjusting to assess the effect of other possible confounders such as sex, age and category of person, there was no significant difference in the hemoglobin determined by the HemoCue compared to Cyanmethemoglobin (coef = -0.127, 95% CI: -0.379 - 0.634). CONCLUSION: Hemoglobin determined by the HemoCue method is comparable to that determined by the other methods. The HemoCue photometer is therefore recommended for use as on-the-spot device for determining hemoglobin in resource poor setting.