Utility of the 4C ISARIC mortality score in hospitalized COVID-19 patients at a large tertiary Saudi Arabian center.

Background: The International Severe Acute Respiratory and Emerging Infections Consortium (ISARIC) 4C mortality score has been used before as a valuable tool for predicting mortality in COVID-19 patients. We aimed to address the utility of the 4C score in a well-defined Saudi population with COVID-19 admitted to a large tertiary referral hospital in Saudi Arabia. Methods: A retrospective study was conducted that included all adults COVID­19 patients admitted to the Armed Forces Hospital Southern Region (AFHSR), between January 2021 and September 2022. The receiver operating characteristic (ROC) curve depicted the diagnostic performance of the 4C Score for mortality prediction. Results: A total of 1,853 patients were enrolled. The ROC curve of the 4C score had an area under the curve of 0.73 (95% CI: 0.702-0.758), p<0.001. The sensitivity and specificity with scores >8 were 80% and 58%, respectively, the positive and negative predictive values were 28% and 93%, respectively. Three hundred and sixteen (17.1%), 638 (34.4%), 814 (43.9%), and 85 (4.6%) patients had low, intermediate, high, and very high values, respectively. There were significant differences between survivors and non-survivors with regard to all variables used in the calculation of the 4C score. Multivariable logistic regression analysis revealed that all components of the 4C score, except gender and O2 saturation, were independent significant predictors of mortality. Conclusions: Our data support previous international and Saudi studies that the 4C mortality score is a reliable tool with good sensitivity and specificity in the mortality prediction of COVID-19 patients. All components of the 4C score, except gender and O2 saturation, were independent significant predictors of mortality. Within the 4C score, odds ratios increased proportionately with an increase in the score value. Future multi-center prospective studies are warranted.

Chloroquine and Hydroxychloroquine for the Prevention and Treatment of COVID-19: A Fiction, Hope or Hype? An Updated Review.

In December 2019, the novel coronavirus disease pandemic (COVID-19) that began in China had infected so far more than 109,217,366 million individuals worldwide and accounted for more than 2,413,912 fatalities. With the dawn of this novel coronavirus (SARS-CoV-2), there was a requirement to select potential therapies that might effectively kill the virus, accelerate the recovery, or decrease the case fatality rate. Besides the currently available antiviral medications for human immunodeficiency virus (HIV) and hepatitis C virus (HCV), the chloroquine/hydroxychloroquine (CQ/HCQ) regimen with or without azithromycin has been repurposed in China and was recommended by the National Health Commission, China in mid-February 2020. By this time, the selection of this regimen was based on its efficacy against the previous SARS-CoV-1 virus and its potential to inhibit viral replication of the SARS-CoV-2 in vitro. There was a shortage of robust clinical proof about the effectiveness of this regimen against the novel SARS-CoV-2. Therefore, extensive research effort has been made by several researchers worldwide to investigate whether this regimen is safe and effective for the management of COVID-19. In this review, we provided a comprehensive overview of the CQ/HCQ regimen, summarizing data from in vitro studies and clinical trials for the protection against or the treatment of SARS-CoV-2. Despite the initial promising results from the in vitro studies and the widespread use of CQ/HCQ in clinical settings during the 1st wave of COVID-19, current data from well-designed randomized controlled trials showed no evidence of benefit from CQ/HCQ supplementation for the treatment or prophylaxis against SARS-CoV-2 infection. Particularly, the two largest randomized controlled trials to date (RECOVERY and WHO SOLIDARITY trials), both confirmed that CQ/HCQ regimen does not provide any clinical benefit for COVID-19 patients. Therefore, we do not recommend the use of this regimen in COVID-19 patients outside the context of clinical trials.

Modifications of Polymers through the Addition of Ultraviolet Absorbers to Reduce the Aging Effect of Accelerated and Natural Irradiation.

The photooxidative degradation process of plastics caused by ultraviolet irradiation leads to bond breaking, crosslinking, the elimination of volatiles, formation of free radicals, and decreases in weight and molecular weight. Photodegradation deteriorates both the mechanical and physical properties of plastics and affects their predicted life use, in particular for applications in harsh environments. Plastics have many benefits, while on the other hand, they have numerous disadvantages, such as photodegradation and photooxidation in harsh environments and the release of toxic substances due to the leaching of some components, which have a negative effect on living organisms. Therefore, attention is paid to the design and use of safe, plastic, ultraviolet stabilizers that do not pose a danger to the environment if released. Plastic ultraviolet photostabilizers act as efficient light screeners (absorbers or pigments), excited-state deactivators (quenchers), hydroperoxide decomposers, and radical scavengers. Ultraviolet absorbers are cheap to produce, can be used in low concentrations, mix well with polymers to produce a homogenous matrix, and do not alter the color of polymers. Recently, polyphosphates, Schiff bases, and organometallic complexes were synthesized and used as potential ultraviolet absorbers for polymeric materials. They reduced the damage caused by accelerated and natural ultraviolet aging, which was confirmed by inspecting the surface morphology of irradiated polymeric films. For example, atomic force microscopy revealed that the roughness factor of polymers' irradiated surfaces was improved significantly in the presence of ultraviolet absorbers. In addition, the investigation of the surface of irradiated polymers using scanning electron microscopy showed a high degree of homogeneity and the appearance of pores that were different in size and shape. The current work surveys for the first time the use of newly synthesized, ultraviolet absorbers as additives to enhance the photostability of polymeric materials and, in particular, polyvinyl chloride and polystyrene, based mainly on our own recent work in the field.

Prevalence and Association of Transfusion Transmitted Infections with ABO and Rh Blood Groups among Blood Donors at the National Blood Bank, Amman, Jordan.

Blood screening is considered a compulsory procedure in health care services to reduce the occurrence of transfusion transmitted infections (TTIs). This study estimated the distribution rates of ABO and Rh blood group systems, prevalence rates of TTIs among blood donors and their association with the ABO blood group and Rh system. A retrospective study was conducted at the national blood bank, Amman, Jordan for a period of 6 years (from January 2013 to December 2018). For TTIs analysis, about 5 mL blood sample was collected from each volunteer. A total of 365,029 persons (346,048 (94.8%) males and 18,981 (5.2%) females) donated their blood at the national blood bank, Amman, Jordan from January 2013 to December 2018. The results revealed that O and A were the most prevalent blood groups (37.44% and 36.82%, respectively), followed by B (18.62%) and AB (7.12%). The distribution of Rh + ve and Rh - ve among blood donors showed that Rh + ve donors were more prevalent (88.73%) compared with Rh - ve (11.27%). HBsAg was the most prevalent viral infection (0.38%) followed by HCV (0.13%), syphilis (0.02%), HIV (0.006%) and the male donors were highly infected when compared with female donors. The association between ABO/Rh blood groups and TTIs infections was nonsignificant. In conclusion, low frequency rates of TTIs among blood donors were detected in the current study, but improvements are still continuously required. Low percentages of female donors need to be managed via conducting health cultural education programs.

Sorption and degradation of ranitidine in soil: Leaching potential assessment.

Pharmaceuticals have been categorized as emerging contaminants that may be hazardous to the environment. To assess their environmental risk, understanding their fate and behaviour is highly needed, particularly in soil where little is known. This study investigated sorption, degradation and mobility potential of ranitidine (RAN) from soil to groundwater in two soils with different physicochemical properties. Sorption resulted in data were found to fit well to isotherm models following the order: linear model > Freundlich > Langmuir with R2 of up to 0.98. RAN showed low sorption affinity to soils with maximum adsorption coefficient (Kd) of 21.47 L kg-1. Physicochemical properties for soil and RAN showed insignificant positive correlation to Kd values except the sand%, which showed significant negative correlation. Degradation of RAN was fitted to the first order exponential decay model with minimum DT50 (time for a 50% dissipation in RAN concentration) values of 31.6 d under non-sterile conditions. Prolonged DT50 of 62.4 d was obtained in soils from sterile treatments indicating the microbial activity role in dissipation of RAN process. To predict potential leaching of RAN in soil, this study experimentally obtained values of Kd, Koc and DT50 were implemented in mathematical screening models. Results showed different but moderate leaching potential of RAN in soils.

Fate, uptake, and distribution of nanoencapsulated pesticides in soil-earthworm systems and implications for environmental risk assessment.

Nanopesticides are novel plant protection products offering numerous benefits. Because nanoparticles behave differently from dissolved chemicals, the environmental risks of these materials could differ from conventional pesticides. We used soil-earthworm systems to compare the fate and uptake of analytical-grade bifenthrin to that of bifenthrin in traditional and nanoencapsulated formulations. Apparent sorption coefficients for bifenthrin were up to 3.8 times lower in the nano treatments than in the non-nano treatments, whereas dissipation half-lives of the nano treatments were up to 2 times longer. Earthworms in the nano treatments accumulated approximately 50% more bifenthrin than those in the non-nano treatments. In the non-nano treatments, most of the accumulated material was found in the earthworm tissue, whereas in the nano treatments, the majority resided in the gut. Evaluation of toxicokinetic modeling approaches showed that models incorporating the release rate of bifenthrin from the nanocapsule and distribution within the earthworm provided the best estimations of uptake from the nano-formulations. Overall, our findings indicate that the risks of nanopesticides may be different from those of conventional formulations. The modeling presented provides a starting point for assessing risks of these materials but needs to be further developed to better consider the behavior of the nanoencapsulated pesticide within the gut system. Environ Toxicol Chem 2018;37:1420-1429. © 2018 SETAC.

Factors affecting the dissipation of pharmaceuticals in freshwater sediments.

Degradation is one of the key processes governing the impact of pharmaceuticals in the aquatic environment. Most studies on the degradation of pharmaceuticals have focused on soil and sludge, with fewer exploring persistence in aquatic sediments. We investigated the dissipation of 6 pharmaceuticals from different therapeutic classes in a range of sediment types. Dissipation of each pharmaceutical was found to follow first-order exponential decay. Half-lives in the sediments ranged from 9.5 (atenolol) to 78.8 (amitriptyline) d. Under sterile conditions, the persistence of pharmaceuticals was considerably longer. Stepwise multiple linear regression analysis was performed to explore the relationships between half-lives of the pharmaceuticals, sediment physicochemical properties, and sorption coefficients for the compounds. Sediment clay, silt, and organic carbon content and microbial activity were the predominant factors related to the degradation rates of diltiazem, cimetidine, and ranitidine. Regression analysis failed to highlight a key property which may be responsible for observed differences in the degradation of the other pharmaceuticals. The present results suggest that the degradation rate of pharmaceuticals in sediments is determined by different factors and processes and does not exclusively depend on a single sediment parameter. Environ Toxicol Chem 2018;37:829-838. © 2017 SETAC.

[Sandflies Fauna of the Focus of Keur Moussa: Current Data on Diversity and Seasonal Variations (Thies, Senegal)]. / Faune phlébotomienne du foyer leishmanien de Keur Moussa : données actuelles sur la diversité et variations saisonnières (Thiès, Sénégal).

An inter-epidemic oversight was conducted in the cutaneous leishmaniasis focus of Keur Moussa (Thies region) between June 2015 and October 2016, more than 20 years after the last epidemic. The three sampling methods (adhesive traps, CDC light traps, and indoor pyrethroids sprays) allowed the capture of 1,746 sand flies belonging to 2 genera and 24 species, those involved in the transmission of leishmaniasis in Senegal, as well as 11 new species for the focus. The vector of human cutaneous leishmaniasis in Senegal, Phlebotomus duboscqi Neveu-Lemaire, 1906, represents 10.9% of this fauna. Sergentomyia schwetzi, one of the species involved, with Sergentomyia dubia and Sergentomyia magna, in the transmission of canine leishmaniasis in Senegal, is the most abundant species with 38.1% of the samples. The other two species have individually smaller percentages. Seasonal variations of the abundance show an intense activity of sandflies at the end of the dry season under the influence of high average temperatures and a humidity exceeding 50%. Rains are a limiting factor. According to the enrichment of the fauna and the high density of the different vectors of leishmaniasis in this focus, particularly P. duboscqi, a specific importance should be given for this focus in order to prevent occurrence of epidemics.

Une surveillance interépidémique a été menée au niveau du foyer de leishmaniose cutanée de Keur Moussa (région de Thiès) entre juin 2015 et octobre 2016, soit plus de 20 ans après la dernière épidémie. Les trois méthodes d'échantillonnage utilisées (papiers huilés, pièges lumineux CDC et pulvérisations intradomiciliaires avec des pyréthrinoïdes) ont permis la capture de 1 746 phlébotomes appartenant à deux genres et 24 espèces, celles impliquées dans la transmission des leishmanioses au Sénégal et 11 espèces nouvelles pour le foyer. Le vecteur de la leishmaniose cutanée humaine au Sénégal, Phlebotomus duboscqi Neveu-Lemaire, 1906, représente 10,9 % des captures. Sergentomyia schwetzi, l'une des espèces impliquées, avec Sergentomyia dubia et Sergentomyia magna, dans la transmission de la leishmaniose canine au Sénégal, est la plus abondante avec 38,1 % des captures. Les deux autres espèces ont des pourcentages individuels moins importants. Les variations saisonnières d'abondance montrent une intense activité des phlébotomes en fin de saison sèche sous l'influence des températures moyennes élevées et d'une humidité dépassant les 50 %. La pluie constitue un facteur limitant. En vue de prévenir la survenue d'épidémies, une importance particulière devra être accordée à ce foyer, vu l'enrichissement de la faune et les densités élevées des différents vecteurs de leishmanioses dans ce foyer, en particulierP. duboscqi.

Impacts of compound properties and sediment characteristics on the sorption behaviour of pharmaceuticals in aquatic systems.

Sorption is a key factor in determining the persistence, attenuation and bioavailability of sediment-associated contaminants. However, our understanding of the sorption behaviour of pharmaceuticals in sediments is poor. In this study, we investigated the sorption behaviour of a diverse set of pharmaceuticals in a range sediment types. Sorption affinity of pharmaceuticals for all sediments was found to increase in the order mefenamic acid

Risk-based prioritization of pharmaceuticals in the natural environment in Iraq.

Numerous studies have demonstrated the occurrence of pharmaceuticals in the natural environment, raising concerns about their impact on non-target organisms or human health. One region where little is known about the exposure and effects of pharmaceuticals in the environment is Iraq. Due to the high number of pharmaceuticals used by the public health sector in Iraq (hospitals and care centres) and distributed over the counter, there is a need for a systematic approach for identifying substances that should be monitored in the environment in Iraq and assessed in terms of environmental risk. In this study, a risk-based prioritization approach was applied to 99 of the most dispensed pharmaceuticals in three Iraqi cities, Baghdad, Mosul and Basrah. Initially, information on the amounts of pharmaceuticals used in Iraq was obtained. The top used medicines were found to be paracetamol, amoxicillin and metformin with total annual consumption exceeding 1000 tonnes per year. Predicted environmental concentrations (PECs) and predicted no-effect concentrations (PNECs), derived from ecotoxicological end-points and effects related to the therapeutic mode of action, were then used to rank the pharmaceuticals in terms of risks to different environmental compartments. Active pharmaceutical ingredients used as antibiotics, antidepressants and analgesics were identified as the highest priority in surface water, sediment and the terrestrial environment. Antibiotics were also prioritized according to their susceptibility to kill or inhibit the growth of bacteria or to accelerate the evolution and dissemination of antibiotic-resistant genes in water. Future work will focus on understanding the occurrence, fate and effects of some of highly prioritized substances in the environment.

Therapeutic effects of inorganic nitrate and nitrite in cardiovascular and metabolic diseases.

Nitric oxide (NO) is generated endogenously by NO synthases to regulate a number of physiological processes including cardiovascular and metabolic functions. A decrease in the production and bioavailability of NO is a hallmark of many major chronic diseases including hypertension, ischaemia-reperfusion injury, atherosclerosis and diabetes. This NO deficiency is mainly caused by dysfunctional NO synthases and increased scavenging of NO by the formation of reactive oxygen species. Inorganic nitrate and nitrite are emerging as substrates for in vivo NO synthase-independent formation of NO bioactivity. These anions are oxidation products of endogenous NO generation and are also present in the diet, with green leafy vegetables having a high nitrate content. The effects of nitrate and nitrite are diverse and include vasodilatation, improved endothelial function, enhanced mitochondrial efficiency and reduced generation of reactive oxygen species. Administration of nitrate or nitrite in animal models of cardiovascular disease shows promising results, and clinical trials are currently ongoing to investigate the therapeutic potential of nitrate and nitrite in hypertension, pulmonary hypertension, peripheral artery disease and myocardial infarction. In addition, the nutritional aspects of the nitrate-nitrite-NO pathway are interesting as diets suggested to protect against cardiovascular disease, such as the Mediterranean diet, are especially high in nitrate. Here, we discuss the potential therapeutic opportunities for nitrate and nitrite in prevention and treatment of cardiovascular and metabolic diseases.

The impact of fish parasites on human health (review article).

One of the most important problems faced by world at the present time is food deficiency. Today the third world is facing protein deficiency as one of the major global challenges. In Egypt, the continuous population explosion requires more food production to meet the consequent increasing demands. However, there are many zoonotic fish parasites not only in Egypt but worldwide.

Higher frequency of genetic variants conferring increased risk for ADRs for commonly used drugs treating cancer, AIDS and tuberculosis in persons of African descent.

There is established clinical evidence for differences in drug response, cure rates and survival outcomes between different ethnic populations, but the causes are poorly understood. Differences in frequencies of functional genetic variants in key drug response and metabolism genes may significantly influence drug response differences in different populations. To assess this, we genotyped 1330 individuals of African (n=372) and European (n=958) descent for 4535 single-nucleotide polymorphisms in 350 key drug absorption, distribution, metabolism, elimination and toxicity genes. Important and remarkable differences in the distribution of genetic variants were observed between Africans and Europeans and among the African populations. These could translate into significant differences in drug efficacy and safety profiles, and also in the required dose to achieve the desired therapeutic effect in different populations. Our data points to the need for population-specific genetic variation in personalizing medicine and care.

Identification and differential expression of two dehydrin cDNAs during maturation of Jatropha curcas seeds.

Plant dehydrin proteins (DHNs) are known to be important for environmental stress tolerance and are involved in various developmental processes. Two full-length cDNAs JcDHN-1 and JcDHN-2 encoding two dehydrins from Jatropha curcas seeds were identified and characterized. JcDHN-1 is 764 bp long and contains an open reading frame of 528 bp. The deduced JcDHN-1 protein has 175 a.a. residues that form a 19.3-kDa polypeptide with a predicted isoelectric point (pI) of 6.41. JcDHN-2 is 855 bp long and contains an open reading frame of 441 bp. The deduced JcDHN-2 protein has 156 a.a. residues that form a 17.1-kDa polypeptide with a predicted pI of 7.09. JcDHN-1 is classified as type Y3SK2 and JcDHN-2 is classified as type Y2SK2 according to the YSK shorthand for structural classification of dehydrins. Homology analysis indicates that both JcDHN-1 and JcDHN-2 share identity with DHNs of other plants. Analysis of the conserved domain revealed that JcDHN-2 has glycoside hydrolase GH20 super-family activity. Quantitative real time PCR analysis for JcDHN-1 and JcDHN-2 expression during seed development showed increasing gene expression of both their transcript levels along with the natural dehydration process during seed development. A sharp increase in JcDHN-2 transcript level occurred in response to water content dropping from 42% in mature seeds to 12% in dry seeds. These results indicate that both JcDHNs have the potential to play a role in cell protection during dehydration occurring naturally during jatropha orthodox seed development.

Traditional herbal antimalarial therapy in Kilifi district, Kenya.

AIM OF STUDY: To identify plant species used by the traditional health practitioners (THPs) in treatment of malaria, carry out cytotoxicity and efficacy evaluation of the identified plants and to evaluate combination effects. MATERIALS AND METHODS: Thirteen plants were selected through interviews with traditional healers. In vitro antiplasmodial testing was done by measuring ability of the test sample to inhibit the incorporation of radio-labelled hypoxanthine into the malaria parasite. The extracts were tested singly and then in combination using the standard fixed ratio analysis to evaluate synergism. In vivo bioassay was done in mice using Peter's 4-days suppressive test and cytotoxicity evaluated in vitro using Vero E6 cells. RESULTS: Of the plants tested in vitro, 25% were highly active (IC(50)<10 µg/ml), 46% moderately active (IC(50) 10-50 µg/ml), 16% had weak activity of 50-100 µg/ml while 13% were not active IC(50) >100 µg/ml. Methanolic extracts of Azadirachta indica, Premna chrysoclada and Uvaria acuminata were the most active (IC(50)<10µg/ml) against both the chloroquine (CQ) sensitive (D6) and the CQ resistant (W2) Plasmodium falciparum clones. When tested in vivo in a mouse model, Azadirachta indica, Rhus natalensis and Grewia plagiophylla depicted the highest percent parasite clearance and chemo suppression of 89%, 82% and 78%, respectively. Evaluating effect of combining some of these extracts with one another against a multi-drug resistant Plasmodium falciparum (W2) clone revealed synergism among some combinations. The highest synergy was between Uvaria acuminata and Premna chrysoclada. The interaction between Grewia plagiophylla and Combretum illairii was largely antagonistic. Impressive cytotoxicity results were obtained with most of the plants tested revealing high selectivity indices an indication of enabling achievement of therapeutic doses at safe concentrations. Uvaria acuminata was, however, toxic to the cultured cells. Mild cytotoxicity was also observed in Hoslundia opposita and Lannea schweinfurthii (CC(50) 37 and 76 µg/ml, respectively). CONCLUSIONS: This study identified plants with low IC(50) values, high percent chemo suppression and low cytotoxicity thus potential sources for novel antiplasmodial agents. The findings remotely justify use of combined medicinal plants in traditional medicine practices as synergy among some plant species was demonstrated.

Blood pressure support in extremely premature infants is affected by different courses of antenatal steroids.

OBJECTIVE: To examine the effects of partial, single and multiple courses of antenatal corticosteroids (ANS) on the need for blood pressure support in extremely premature infants. METHODS: Extremely premature infants with gestational age of 24 to 28 weeks were included in this study during a 5-year period. The main outcome measure of the study was the amount of blood pressure support during the first 3 days of life. RESULTS: The study infants (n = 163) were divided into: infants not exposed (ANS; n = 27) and exposed to ANS (ANS; n = 136). Blood pressure support was significantly lower in ANS compared with No ANS (65% vs 96%; p = 0.003) and in single course (SANS; n = 73) and >or=2 courses (MANS; n = 34) compared with partial course of ANS (PANS; n = 29) (62%, 56% vs 86%; p = 0.03). The number of infants who received volume support and the amount of volume support were significantly lower in ANS compared with that in No ANS (p < 0.001) and in SANS and MANS compared with that in PANS (p < 0.02). CONCLUSION: Exposure to multiple courses of ANS was as beneficial as single course of ANS in decreasing the need for blood pressure support in extremely premature infants.

Anti-plasmodial activity of the extracts of some Kenyan medicinal plants.

ETHNOPHARMACOLOGICAL RELEVANCE: The spread of drug resistant Plasmodium falciparum strains necessitates search for alternative newer drugs for use against malaria. Medicinal plants used traditionally in preparation of herbal medicines for malaria are potential source of new anti-malarial drugs. AIM OF THE STUDY: To identify the anti-plasmodial potential of twelve plants used in preparing herbal remedies for malaria in Kilifi and Tharaka districts of Kenya. MATERIALS AND METHODS: Twelve plants used traditionally for anti-malarial therapy in Kilifi and Tharaka districts were extracted with water/methanol yielding twenty-three extracts. The extracts were tested against chloroquine sensitive (NF54) and resistant (ENT30) P. falciparum strains in vitro using (3)Hypoxanthine assay. RESULTS: Seven (30%) extracts showed activity against P. falciparum with IC(50) values below 20 microg/ml. The remaining 16 extracts showed low or no activity. The most active extracts were from Zanthoxylum chalybeum (Rutaceae) with an IC(50) value of 3.65 microg/ml, Cyperus articulatus (Cyperaceae) with 4.84mug/ml, and Cissampelos pareira (Menispermaceae) with 5.85 microg/ml. CONCLUSIONS: This study revealed plants, that are potential sources of anti-malarial compounds. Anti-plasmodial activities of extracts of T. simplicifolia, C. pareira, and C. articulatus are reported for the first time.

Anti-plasmodial activity of the extracts and two sesquiterpenes from Cyperus articulatus.

Two sesquiterpenes, corymbolone and mustakone, isolated from the chloroform extract of the rhizomes of Cyperus articulatus, exhibited significant anti-plasmodial properties. Mustakone was approximately ten times more active than corymbolone against the sensitive strains of the Plasmodium falciparum.