Sickle cell disease in the Zanzibar Archipelago, the Republic of Tanzania.

BACKGROUND: Sickle cell disease (SCD) is one of the most severe haemoglobinopathies, a group of blood disorders, typically inherited. The condition affects over 7.7 million people globally and results in more than 370,000 deaths per year. The highest morbidity and mortality rates are seen in Africa and most children with SCD are born in Tanzania. The available literature on SCD morbidity in Tanzania focus primarily on the residents of the mainland, while there is little data available on SCD morbidity among residents of the Tanzanian islands in the Indian Ocean. The aim of the present study was to confirm the presence of sickle cell disease among residents of the Zanzibar Archipelago. MATERIAL AND METHODS: The study group consisted of 27 people, residents of Pemba Island in the Zanzibar Archipelago, aged between 2 months and 26 years old, whose at least one parent has been diagnosed with sickle cell anaemia. Blood samples collected from the study participants were tested using HemoTypeSCTM, a rapid, point-of-care diagnostic test. The tests were performed at the Amal Hospital (Chake Chake town, Pemba Island) in June 2023. RESULTS: Sickle cell disease was diagnosed in 11 study subjects (40.7%); their haemoglobin concentration ranged between 6.6 and 8.5 g/dL. The presence of the sickle cell trait (HbAS phenotype) was confirmed in 14 patients (51.9%). Only two of the tested patients had normal haemoglobin phenotype. CONCLUSIONS: The results of the present study support the necessity to introduce large-scale population- -based screening for SCD in the Zanzibar Archipelago, especially in infants whose family members have sickle cell anaemia. The introduction of such a programme will help monitor the number of new SCD cases in the region and may potentially reduce infant mortality due to SCD as well as minimize complications from SCD in older children through the adoption of effective disease prevention measures.

The impact of gastrointestinal tract infection on acquiring dengue fever virus infection and haemorrhagic fever in Jeddah region, Saudi Arabia.

This study aimed to investigate the relationship between gastrointestinal tract infection and dengue hemorrhagic fever. Dengue hemorrhagic fever is a syndrome caused by the dengue virus and primarily affects children below ten years of age and is spread by the Aedes aegypti mosquito. Gastrointestinal tract infection is a bacterial and parasitic infection that leads to gastrointestinal tract inflammation which involves the small intestine and the stomach. The relationship between the two can be manifested by gastrointestinal bleeding, acute pancreatitis, and fulminant liver failure. In this research work, 600 blood and feces samples of different ages and sex (7-8 worms) were collected from Jeddah city. From the blood samples, serum was made and stored at -20°C until use. The frozen sera samples were investigated for sero-detection of DENV-NS1 antigen as a rapid, sensitive, and cost-effective test to detect asymptomatic acute DENV-infected donors and anti-DENV IgM and IgG antibodies. Feces samples were processed for the detection of parasites. The data acquired from these samples of all the 600 participants were analyzed and interpreted, followed by statistical analysis using GraphPad Prism 5.0 software. All the values were considered significant, which showed a value of less than 0.05. Results were expressed as with the range. This article documents that gastrointestinal tract manifestations frequently occur among patients with dengue hemorrhagic fever. There are close relationships between gastrointestinal tract infection and dengue hemorrhagic fever. In current work, it was established that dengue fever leads to gastrointestinal tract bleeding in the presence of intestinal parasites. Therefore, failure to identify the patients with this infection early enough can lead to an increased morbidity and mortality rate.

Investigating the N-shape EKC using capture fisheries as a biodiversity indicator: empirical evidence from selected 14 emerging countries.

The majority of studies investigating the environmental Kuznets curve predominantly focus on atmospheric indicators, thereby neglecting other environmental indicators such as land, sea, coastal, coral reefs, freshwater, and biodiversity indicators. This study aims to examine the environmental Kuznets curve by using capture fisheries production as a biodiversity indicator. The study uses a panel of 14 countries, of which 10 are newly industrialized and the other 4 are fast-emerging countries. The study applies the CADF and CIPS unit root tests to identify the integration order as proposed by Pesaran (2007). After identifying the unique order of integration, the Westerlund (2007) panel cointegration is applied. A long-run relationship is confirmed among the variables. The study revealed that an N-pattern relationship exists between capture fisheries production (CFP) and growth of the economy in the panel of selected countries. The industry focuses on achieving a cleaner environment and promotes the sustainable development of the fisheries. Financial development has a negative and significant effect on CFP. This reflects that domestic credit is not only used for the capture of fish but also for conservation purposes. The exports of goods and services have a positive relationship with CFP, while imports have a negative and significant effect on CFP. Policies to promote investments in the conservation of fisheries should be implemented, and credit creation should be directed by appropriate legislation to ensure the conservation of biodiversity and environmental sustainability.

Exploring the role of fossil fuels, hydroelectricity consumption, and financial sector in ensuring sustainable economic development in the emerging economy.

This study is conducted to address the research question of whether hydroelectricity and fossil fuels contribute to sustainable economic development in an emerging economy in this era of globalization? Further, this study applies the novel approach of Harvey unit root test which is a linearity test to predict the possible existence of non-linearity. The results confirmed that the majority of the series in this study are linear. Furthermore, the two break test is applied to investigate the integration sequence of the series. The bounds test approach confirms the existence of a long-run association among the variables. Additionally, the long-run relationship is analysed within the framework of the ARDL approach. Financial development, fossil fuel, and capital positively contribute to economic development, while the effect of hydroelectricity is insignificant. Moreover, globalization effects GDP negatively. The symmetric causality suggests a uni-directional causal movement from hydroelectricity consumption and globalization towards GDP. The outcome of the study emphasizes the importance of renewable sources such as hydropower energy for ensuring sustainable development in the presence of globalization.

Trauma-Informed Care and Cultural Humility in the Mental Health Care of People From Minoritized Communities.

The prevalence and impact of trauma constitute a public health crisis that is complicated by the cultural heterogeneity of contemporary society and a higher rate of trauma among individuals from minoritized communities. A trauma-informed care approach can facilitate improved treatment of those who have experienced trauma, and trauma-informed care is increasingly viewed as potentially beneficial for all patients. This article outlines general principles of trauma-informed care and ways to enact it. Because the situations in which trauma arises, the ways in which it is conceptualized, and how patients respond to it are influenced by both culture and individual factors, a cultural humility approach is also described and recommended. Psychiatrists can navigate the complex terrain of cultures and social backgrounds in the clinical encounter and can promote healing when treating patients who have experienced trauma by adopting a trauma-informed care approach and an attitude of cultural humility.

Mesenchymal Stem Cells Loaded with p5, Derived from CDK5 Activator p35, Inhibit Calcium-Induced CDK5 Activation in Endothelial Cells.

The potential use of stem cells as therapeutics in disease has gained momentum over the last few years and recently phase-I clinical trials have shown favourable results in treatment of a small cohort of acute stroke patients. Similarly, they have been used in preclinical models drug-loaded for the effective treatment of solid tumours. Here we have characterized uptake and release of a novel p5-cyclin-dependent kinase 5 (CDK5) inhibitory peptide by mesenchymal stem cells and showed release levels capable of blocking aberrant cyclin-dependent kinase 5 (CDK5) signaling pathways, through phosphorylation of cyclin-dependent kinase 5 (CDK5) and p53. These pathways represent the major acute mechanism stimulating apoptosis after stroke and hence its modulation could benefit patient recovery. This work indicates a potential use for drug-loaded stem cells as delivery vehicles for stroke therapeutics and in addition as anticancer receptacles particularly, if a targeting and/or holding mechanism can be defined.

The psychopharmacology algorithm project at the Harvard South Shore Program: an algorithm for acute mania.

This new algorithm for the pharmacotherapy of acute mania was developed by the Psychopharmacology Algorithm Project at the Harvard South Shore Program. The authors conducted a literature search in PubMed and reviewed key studies, other algorithms and guidelines, and their references. Treatments were prioritized considering three main considerations: (1) effectiveness in treating the current episode, (2) preventing potential relapses to depression, and (3) minimizing side effects over the short and long term. The algorithm presupposes that clinicians have made an accurate diagnosis, decided how to manage contributing medical causes (including substance misuse), discontinued antidepressants, and considered the patient's childbearing potential. We propose different algorithms for mixed and nonmixed mania. Patients with mixed mania may be treated first with a second-generation antipsychotic, of which the first choice is quetiapine because of its greater efficacy for depressive symptoms and episodes in bipolar disorder. Valproate and then either lithium or carbamazepine may be added. For nonmixed mania, lithium is the first-line recommendation. A second-generation antipsychotic can be added. Again, quetiapine is favored, but if quetiapine is unacceptable, risperidone is the next choice. Olanzapine is not considered a first-line treatment due to its long-term side effects, but it could be second-line. If the patient, whether mixed or nonmixed, is still refractory to the above medications, then depending on what has already been tried, consider carbamazepine, haloperidol, olanzapine, risperidone, and valproate first tier; aripiprazole, asenapine, and ziprasidone second tier; and clozapine third tier (because of its weaker evidence base and greater side effects). Electroconvulsive therapy may be considered at any point in the algorithm if the patient has a history of positive response or is intolerant of medications.

N400 in schizophrenia patients.

PURPOSE OF REVIEW: The purpose of this article is to review major findings in event related potential (ERP) research in schizophrenia patients, specifically focusing on the N400 component. RECENT FINDINGS: Patients with chronic schizophrenia have difficulty using 'context' (understanding the meaning of the word relative to the sentence) in sentence processing studies and often show differences from control populations in language experiments using word priming. Both of these observations are associated with an abnormal N400 ERP component when compared with nonpsychotic individuals. Many studies of language function rely on priming paradigms that use pairs of words such that the first word in a pair is a 'prime' and a second word in a pair is a 'target', separated from the prime by a period of time known as the Stimulus Onset Asynchrony (SOA). If the SOA is short (i.e., below 400 ms) then it is believed that a priming study examines primarily processes of initial activation within semantic networks; if it is long (i.e., more than 400 ms) then it is believed that a priming study examines primarily processes of context use, generating predictions and matching these predictions against upcoming semantic information. Priming paradigms that use long SOAs are consistently associated with a more negative N400 (hence lack of priming) in schizophrenia, whereas priming paradigms using a short SOA produce either a normal N400 priming response or hyperpriming as shown by a reduced N400 and related to a hypothesized too rapid automatic spread of activation within the semantic memory pathway. Apparent differences among reported study results are likely due to paradigm differences that tap into different aspects of language processing. Although the presence of both hyperactivation within semantic networks and difficulties with the use of context is well known in schizophrenia, it is unclear whether these abnormalities are also present prior to illness onset in people who are at risk for development of schizophrenia or even present at the onset of illness. SUMMARY: In order to clarify the findings reviewed here, future studies will be needed that focus on examining the N400 response in young people at high risk for developing the illness using multiple paradigms that probe different aspects of language function.

Cobinamide is superior to other treatments in a mouse model of cyanide poisoning.

CONTEXT: Cyanide is a rapidly acting cellular poison, primarily targeting cytochrome c oxidase, and is a common occupational and residential toxin, mostly via smoke inhalation. Cyanide is also a potential weapon of mass destruction, with recent credible threats of attacks focusing the need for better treatments, as current cyanide antidotes are limited and impractical for rapid deployment in mass casualty settings. OBJECTIVE: We have used mouse models of cyanide poisoning to compare the efficacy of cobinamide (Cbi), the precursor to cobalamin (vitamin B(12)), to currently approved cyanide antidotes. Cbi has extremely high affinity for cyanide and substantial solubility in water. MATERIALS AND METHODS: We studied Cbi in both an inhaled and intraperitoneal model of cyanide poisoning in mice. RESULTS: We found Cbi more effective than hydroxocobalamin, sodium thiosulfate, sodium nitrite, and the combination of sodium thiosulfate-sodium nitrite in treating cyanide poisoning. Compared to hydroxocobalamin, Cbi was 3 and 11 times more potent in the intraperitoneal and inhalation models, respectively. Cobinamide sulfite (Cbi-SO(3)) was rapidly absorbed after intramuscular injection, and mice recovered from a lethal dose of cyanide even when given at a time when they had been apneic for over 2 min. In range-finding studies, Cbi-SO(3) at doses up to 2000 mg/kg exhibited no clinical toxicity. DISCUSSION AND CONCLUSION: These studies demonstrate that Cbi is a highly effective cyanide antidote in mouse models, and suggest it could be used in a mass casualty setting, because it can be given rapidly as an intramuscular injection when administered as Cbi-SO(3). Based on these animal data Cbi-SO(3) appears to be an antidote worthy of further testing as a therapy for mass casualties.

Comparison of cobinamide to hydroxocobalamin in reversing cyanide physiologic effects in rabbits using diffuse optical spectroscopy monitoring.

Our purpose is to compare cobinamide to hydroxocobalamin in reversing cyanide (CN)-induced physiologic effects in an animal model using diffuse optical spectroscopy (DOS). Cyanide poisoning is a major threat worldwide. Cobinamide is a novel molecule that can bind two molecules of cyanide, has a much higher binding affinity than hydroxocobalamin, and is more water soluble. We investigated the ability of equimolar doses of cobinamide and hydroxocobalamin to reverse the effects of cyanide exposure in an animal model monitored continuously by DOS. Cyanide toxicity was induced in 16 New Zealand white rabbits by intravenous infusion. Animals were divided into three groups: controls (n=5) received saline following cyanide, hydroxocobalamin (N=6) following cyanide, and cobinamide (N=5) following cyanide. Cobinamide caused significantly faster and more complete recovery of oxy- and deoxyhemoglobin concentrations in cyanide-exposed animals than hydroxocobalamin- or saline-treated animals, with a recovery time constant of 13.8+/-7.1 min compared to 75.4+/-25.1 and 76.4+/-42.7 min, for hydroxocobalamin- and saline-treated animals, respectively (p<0.0001). This study indicates that cobinamide more rapidly and completely reverses the physiologic effects of cyanide than equimolar doses of cobalamin at the dose used in this study, and CN effects and response can be followed noninvasively using DOS.

Intramuscular cobinamide sulfite in a rabbit model of sublethal cyanide toxicity.

STUDY OBJECTIVE: Exposure to cyanide in fires and industrial exposures and intentional cyanide poisoning by terrorists leading to mass casualties is an ongoing threat. Current treatments for cyanide poisoning must be administered intravenously, and no rapid treatment methods are available for mass casualty cyanide exposures. Cobinamide is a cobalamin (vitamin B(12)) analog with an extraordinarily high affinity for cyanide that is more water-soluble than cobalamin. We investigate the use of intramuscular cobinamide sulfite to reverse cyanide toxicity-induced physiologic changes in a sublethal cyanide exposure animal model and determine the ability of an intramuscular cobinamide sulfite injection to rapidly reverse the physiologic effects of cyanide toxicity. METHODS: New Zealand white rabbits were given 10 mg sodium cyanide intravenously over 60 minutes. Quantitative diffuse optical spectroscopy and continuous-wave near-infrared spectroscopy monitoring of tissue oxyhemoglobin and deoxyhemoglobin concentrations were performed concurrently with blood cyanide level measurements and cobinamide levels. Immediately after completion of the cyanide infusion, the rabbits were injected intramuscularly with cobinamide sulfite (n=6) or inactive vehicle (controls, n=5). RESULTS: Intramuscular administration led to rapid mobilization of cobinamide and was extremely effective at reversing the physiologic effects of cyanide on oxyhemoglobin and within deoxyhemoglobin extraction. Recovery time to 63% of their baseline values in the central nervous system occurred within a mean of 1,032 minutes in the control group and 9 minutes in the cobinamide group, with a difference of 1,023 minutes (95% confidence interval 116 to 1,874 minutes). In muscle tissue, recovery times were 76 and 24 minutes, with a difference of 52 minutes (95% confidence interval 7 to 98 minutes). RBC cyanide levels returned toward normal significantly faster in cobinamide sulfite-treated animals than in control animals. CONCLUSION: Intramuscular cobinamide sulfite rapidly and effectively reverses the physiologic effects of cyanide poisoning, suggesting that a compact cyanide antidote kit can be developed for mass casualty cyanide exposures.

Association between XRCC1 G399A Polymorphism and Late Complications to Radiotherapy in Saudi Head and Neck Cancer Patients.

BACKGROUND: It has been hypothesized that patient to patient variation in normal tissue reactions to radiotherapy is associated with the presence of polymorphic variations in genes involved in DNA repair. PURPOSE: To test for a possible association between two single-nucleotide polymorphisms (SNPs), XRCC1 399 G>A Arg/Gln and XRCC3 241 C>T Thr/Met and late reactions to radiotherapy. PATIENTS AND METHODS: In this case control study, 50 Head and Neck cancer patients were retrospectively recruited. The grade (G) of fibrosis, a late complication to radiotherapy, was scored using the RTOG/EORTC grading system. Radiosensitive patients with moderate to severe subcutaneous and deep tissue fibrosis (cases, G2-3, n=25) where matched with patients with minimal fibrotic reactions (control, G0-1, n=25). The two nonsynonymous SNPs were genotyped by direct sequencing of DNA extracted from blood or cultured fibroblasts. RESULTS: Allelic frequency showed significant association with grade of fibrosis for XRCC1 399 G/A (p=0.05), but not for XRCC3 241 C>T (p=0.10). CONCLUSIONS: This pilot study corroborates the association between XRCC1 399 G>A and risk of late normal tissue complications following radiotherapy in our patients. Large studies are required to unravel more SNPs that can influence radiosensitivity and ascertain the associations with reactions to radiotherapy in order to be used as genetic predictive biomarkers of individual radiosensitivity. KEY WORDS: Single nucleotide polymorphism - Radiosensitivity - Late reactions to radiotherapy - XRCC1 - XRCC3.