Changing the Landscape of Solid Tumor Therapy from Apoptosis-Promoting to Apoptosis-Inhibiting Strategies.

The many limitations of implementing anticancer strategies under the term "precision oncology" have been extensively discussed. While some authors propose promising future directions, others are less optimistic and use phrases such as illusion, hype, and false hypotheses. The reality is revealed by practicing clinicians and cancer patients in various online publications, one of which has stated that "in the quest for the next cancer cure, few researchers bother to look back at the graveyard of failed medicines to figure out what went wrong". The message is clear: Novel therapeutic strategies with catchy names (e.g., synthetic "lethality") have not fulfilled their promises despite decades of extensive research and clinical trials. The main purpose of this review is to discuss key challenges in solid tumor therapy that surprisingly continue to be overlooked by the Nomenclature Committee on Cell Death (NCCD) and numerous other authors. These challenges include: The impact of chemotherapy-induced genome chaos (e.g., multinucleation) on resistance and relapse, oncogenic function of caspase 3, cancer cell anastasis (recovery from late stages of apoptosis), and pitfalls of ubiquitously used preclinical chemosensitivity assays (e.g., cell "viability" and tumor growth delay studies in live animals) that score such pro-survival responses as "lethal" events. The studies outlined herein underscore the need for new directions in the management of solid tumors.

Comparison of BD Phoenix and disk diffusion to broth microdilution for determining cefepime susceptibility among carbapenem-resistant Enterobacterales.

There are increasing reports of carbapenem-resistant Enterobacterales (CRE) that test as cefepime-susceptible (S) or susceptible-dose dependent (SDD). However, there are no data to compare the cefepime testing performance of BD Phoenix automated susceptibility system (BD Phoenix) and disk diffusion (DD) relative to reference broth microdilution (BMD) against carbapenemase-producing (CPblaKPC-CRE) and non-producing (non-CP CRE) isolates. Cefepime susceptibility results were interpreted according to CLSI M100Ed32. Essential agreement (EA), categorical agreement (CA), minor errors (miEs), major errors (MEs), and very major errors (VMEs) were calculated for BD Phoenix (NMIC-306 Gram-negative panel) and DD relative to BMD. Correlates were also analyzed by the error rate-bounded method. EA and CA for CPblaKPC-CRE isolates (n = 64) were <90% with BD Phoenix while among non-CP CRE isolates (n = 58), EA and CA were 96.6%, and 79.3%, respectively. CA was <90% with DD for both cohorts. No ME or VME was observed for either isolate cohort; however, miEs were >10% for CPblaKPC-CRE and non-CP CRE with BD Phoenix and DD tests. For error rate-bounded method, miEs were <40% for IHigh + 1 to ILow - 1 ranges for CPblaKPC-CRE and non-CP CRE with BD Phoenix. Regarding disk diffusion, miEs were unacceptable for all MIC ranges among CPblaKPC-CRE. For non-CP CRE isolates, only IHigh + 1 to ILow - 1 range was acceptable at 37.2%. Using this challenge set of genotypic-phenotypic discordant CRE, the BD Phoenix MICs and DD susceptibility results trended higher (toward SDD and resistant phenotypes) relative to reference BMD results yielding lower CA. These results were more prominent among CPblaKPC-CRE than non-CP CRE.

Performance comparison of BD Phoenix CPO detect panel with Cepheid Xpert Carba-R assay for the detection of carbapenemase-producing Klebsiella pneumoniae isolates.

BACKGROUND: We aimed to compare the performance of carbapenemase classification in carbapenem-resistant Klebsiella pneumoniae (CRKP) obtained using the BD Phoenix CPO Detect panel (CPO panel) and Cepheid Xpert Carba-R assays. We analyzed 55 CRKP strains from clinical specimens collected between November 2020 and November 2022. The CPO panel was used to detect both antibiotic susceptibility and phenotypic carbapenemase classes, while Xpert Carba-R was employed to identify KPC, NDM, VIM, OXA-48, and IMP genes. Due to the limited availability of molecular kits, we arbitrarily selected 55 isolates, identified as carbapenemase-producing according to the CPO panel and with meropenem minimum inhibitory concentration values > 8 mg/L. RESULTS: According to the Xpert Carba-R assay, 16 of the 55 isolates (29.1%) were categorised as Ambler Class A (11 of which matched CPO panel Class A identification); three isolates (5.5%) were identified as Class B and 27 isolates (49.1%) as Class D (in both cases consistent with CPO panel B and D classifications). A further eight isolates (14.5%) exhibited multiple carbapenemase enzymes and were designated as dual-carbapenemase producers, while one isolate (1.8%) was identified as a non-carbapenemase-producer. The CPO panel demonstrated positive and negative percent agreements of 100% and 85.7% for Ambler Class A, 100% and 100% for Class B, and 96.4% and 100% for Class D carbapenemase detection, respectively. CONCLUSION: While the CPO panel's phenotypic performance was satisfactory in detecting Class B and D carbapenemases, additional confirmatory testing may be necessary for Class A carbapenemases as part of routine laboratory procedures.

Date (Phoenix dactylifera L. Mill) fruit enhances sexual performance via modulation of oxido-inflammatory mediators and purinergic signaling in hypertensive male rats.

INTRODUCTION: The present study aimed at investigating the effect of dietary supplementation of Phoenix dactylifera, an important component of aphrodisiac supplements, on sexual performance, oxido-inflammatory mediators and purinergic signaling system in hypertensive rats. MATERIAL AND METHODS: Hypertension was induced via oral administration of 40 mg/kg L-NAME. Thereafter, the sexual performance of the experimental animals was determined and the hypertensive rats with impaired sexual activities were placed on P. dactylifera-supplemented diet for 21 days, and the effects of the treatment on the overall sexual behavior, antioxidant status, oxido-inflammatory biomarkers, and enzyme activity of the purinergic system were assessed. RESULTS: Hypertensive rats showed a significant (p < 0.05) decrease in sexual performance, elevated level of oxido-inflammatory mediators, and altered purinergic enzymes activity when compared with the control. However, sub-chronic feeding with P. dactylifera-supplemented diet improved sexual performance, significantly lowered oxido-inflammatory biomarkers, and enhanced the activity of purinergic enzymes in hypertensive rats. CONCLUSION: Findings presented in this study suggest that dietary inclusion of P. dactylifera could be useful in managing erectile dysfunction (ED) commonly observed in subjects with hypertension. Findings highlighted in this study thus provide the scientific basis supporting the folkloric use of P. dactylifera as a key ingredient in aphrodisiac supplements.

Exploring the Influence of Date Palm Cultivars on Soil Microbiota.

Plants thrive in diverse environments, where root-microbe interactions play a pivotal role. Date palm (Phoenix dactylifera L.), with its genetic diversity and resilience, is an ideal model for studying microbial adaptation to different genotypes and stresses. This study aimed to analyze the bacterial and fungal communities associated with traditional date palm cultivars and the widely cultivated "Deglet Nour" were explored using metabarcoding approaches. The microbial diversity analysis identified a rich community with 13,189 bacterial and 6442 fungal Amplicon Sequence Variants (ASVs). Actinobacteriota, Proteobacteria, and Bacteroidota dominated bacterial communities, while Ascomycota dominated fungal communities. Analysis of the microbial community revealed the emergence of two distinct clusters correlating with specific date palm cultivars, but fungal communities showed higher sensitivity to date palm genotype variations compared to bacterial communities. The commercial cultivar "Deglet Nour" exhibited a unique microbial composition enriched in pathogenic fungal taxa, which was correlated with its genetic distance. Overall, our study contributes to understanding the complex interactions between date palm genotypes and soil microbiota, highlighting the genotype role in microbial community structure, particularly among fungi. These findings suggest correlations between date palm genotype, stress tolerance, and microbial assembly, with implications for plant health and resilience. Further research is needed to elucidate genotype-specific microbial interactions and their role in enhancing plant resilience to environmental stresses.

Health implications of urban tree canopy policy scenarios in Denver and Phoenix: A quantitative health impact assessment.

BACKGROUND: Urban tree canopy (UTC) goals are a popular policy to increase urban vegetation, support climate strategies, and encourage a healthy environment. Health studies related to UTC are needed across cities to support evidence-based decision-making. METHODS: We used a quantitative Health Impact Assessment (HIA) to model the annual number of premature deaths prevented, and the number of stroke and dementia cases, under UTC goals in Denver, Colorado, and Phoenix, Arizona, USA, using standing policy goals (20% and 25% UTC, respectively) and 50% ("half-way") attainment scenarios from current levels (16.5% and 13% UTC, respectively), using publicly accessible national datasets, and a proportional representation of UTC change to standardize across methodologies. We estimated UTC health impacts by relating UTC with scenario-based changes in the Normalized Difference Vegetation Index (NDVI) and considered health equity in UTC distributions and benefits. RESULTS: We projected that at 2020 populations, uniform 20% UTC attainment across Denver block groups would avert 200 (95% uncertainty interval: (UI) 100, 306) annual premature deaths among adults 18 and older, along with 4.1 (95% UI: 2.2, 6.7) annual cases of stroke (adults ≥35), and 2.6 (95% UI: 1.5, 4.1) cases of dementia (adults ≥65), with "halfway" attainment from current levels (16.5% UTC) capturing ∼64% of these benefits. In Phoenix, uniform 25% UTC would annually prevent 368 (95% UI: 181, 558) premature deaths, 8.7 (95% UI: 4.7, 13.9) cases of stroke, and 5,1 (95% UI: 2.9, 8.0) of dementia, with the "halfway" scenario (17% UTC) achieving ∼44% of these results. Both cities saw significantly different greenspace exposures and health outcomes by socioeconomic vulnerability. Denver had more spatially and socioeconomically heterogeneous projected health benefits than Phoenix. CONCLUSIONS: Implementing UTC goals can prevent excess mortality and chronic diseases among urban residents. UTC goals can be used as a health promotion and prevention tool.

Comparative genomics reveals insights into the potential of Lysinibacillus irui as a plant growth promoter.

Members of the genus Lysinibacillus attract attention for their mosquitocidal, bioremediation, and plant growth-promoting abilities. Despite this interest, comprehensive studies focusing on genomic traits governing plant growth and stress resilience in this genus using whole-genome sequencing are still scarce. Therefore, we sequenced and compared the genomes of three endophytic Lysinibacillus irui strains isolated from Canary Island date palms with the ex-type strain IRB4-01. Overall, the genomes of these strains consist of a circular chromosome with an average size of 4.6 Mb and a GC content of 37.2%. Comparative analysis identified conserved gene clusters within the core genome involved in iron acquisition, phosphate solubilization, indole-3-acetic acid biosynthesis, and volatile compounds. In addition, genome analysis revealed the presence of genes encoding carbohydrate-active enzymes, and proteins that confer resistance to oxidative, osmotic, and salinity stresses. Furthermore, pathways of putative novel bacteriocins were identified in all genomes. This illustrates possible common plant growth-promoting traits shared among all strains of L. irui. Our findings highlight a rich repertoire of genes associated with plant lifestyles, suggesting significant potential for developing inoculants to enhance plant growth and resilience. This study is the first to provide insights into the overall genomic signatures and mechanisms of plant growth promotion and biocontrol in the genus Lysinibacillus. KEY POINTS: • Pioneer study in elucidating plant growth promoting in L. irui through comparative genomics. • Genome mining identified biosynthetic pathways of putative novel bacteriocins. • Future research directions to develop L. irui-based biofertilizers for sustainable agriculture.

Phoenix criteria for sepsis: are these enough to guide a clinician?

Sepsis is the leading cause of mortality in children worldwide. There is a paucity of data on the criteria used to define sepsis and septic shock and predict mortality. Schlapbach et al. published Phoenix criteria to define sepsis in JAMA in 2024. Previously, paediatricians have used systemic inflammatory response syndrome (SIRS) criteria, but these criteria lack sensitivity and specificity. This group recommends that sepsis in children be identified by a Phoenix Sepsis Score of at least 2 points in children with suspected infection, which indicates potentially life-threatening dysfunction of the respiratory, cardiovascular, coagulation, and/or neurological systems. Though included in the 8-point criteria, important criteria like renal and liver are missing from the main criteria. We remain worried about the way these criteria got excluded from the main criteria. Therefore, in this brief report, whilst commending the authors for this stelar task, we highlight the main pitfalls in these criteria especially the renal, neurologic, and liver criteria. These criteria have been shown to be independently associated with outcomes, and we recommend that in the future iterations of the criteria, renal and liver criteria should be defined according to latest definitions and the task force consider utilizing latest criteria for each organ system involved within the formulated criteria. CONCLUSION:  In conclusion, Phoenix criteria are a step in the right direction to define life-threatening organ dysfunction in sepsis, but clinicians need to be mindful that diagnosis/treatment of less severe sepsis should not be delayed if these criteria are not met. Therefore, local early detection and management tools for sepsis should be followed. WHAT IS KNOWN: • There has always been a quest for a definition for pediatric sepsis. There are limitations to the previous pediatric sepsis criteria which were published in 2005 by the International Pediatric Sepsis Consensus Conference (IPSCC). IPSCC defines sepsis as a suspected or confirmed infection in the presence of systemic inflammatory response syndrome (SIRS). These new Phoenix Pediatric Sepsis (PPS) criteria for sepsis and septic shock are intended to identify children with life-threatening organ dysfunction due to infection, and the score was developed based on a very large pediatric dataset. WHAT IS NEW: • Though the intention of Phoenix criteria is to help identify children with life threatening organ dysfunction, unfortunately the crietria will miss signs of early sepis. In this manuscript, we point out some of the drawbacks of these criteria which need to be borne in mind while applying these criteria.

Is oral consumption of dates (Phoenix dactylifera L. fruit) in the peripartum period effective and safe integrative care to facilitate childbirth and improve perinatal outcomes: a comprehensive revised systematic review and dose-response meta-analysis.

BACKGROUND: Recent reviews have reported inconclusive results regarding the usefulness of consuming dates (Phoenix dactylifera L. fruit) in the peripartum period. Hence, this updated systematic review with meta-analysis sought to investigate the efficacy and safety of this integrated intervention in facilitating childbirth and improving perinatal outcomes. METHODS: Eight data sources were searched comprehensively from their inception until April 30, 2023. Parallel-group randomized and non-randomized controlled trials published in any language were included if conducted during peripartum (i.e., third trimester of pregnancy, late pregnancy, labor, or postpartum) to assess standard care plus oral consumption of dates versus standard care alone or combined with other alternative interventions. The Cochrane Collaboration's Risk of Bias (RoB) assessment tools and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) were employed to evaluate the potential RoB and the overall quality of the evidence, respectively. Sufficient data were pooled by a random-effect approach utilizing Stata software. RESULTS: Of 2,460 records in the initial search, 48 studies reported in 55 publications were included. Data were insufficient for meta-analysis regarding fetal, neonatal, or infant outcomes; nonetheless, most outcomes were not substantially different between dates consumer and standard care groups. However, meta-analyses revealed that dates consumption in late pregnancy significantly shortened the length of gestation and labor, except for the second labor stage; declined the need for labor induction; accelerated spontaneity of delivery; raised cervical dilatation (CD) upon admission, Bishop score, and frequency of spontaneous vaginal delivery. The dates intake in labor also significantly reduced labor duration, except for the third labor stage, and increased CD two hours post-intervention. Moreover, the intervention during postpartum significantly boosted the breast milk quantity and reduced post-delivery hemorrhage. Likewise, dates supplementation in the third trimester of pregnancy significantly increased maternal hemoglobin levels. The overall evidence quality was also unacceptable, and RoB was high in most studies. Furthermore, the intervention's safety was recorded only in four trials. CONCLUSION: More well-designed investigations are required to robustly support consuming dates during peripartum as effective and safe integrated care. TRIAL REGISTRATION: PROSPERO Registration No: CRD42023399626.

Carbapenem non-susceptibility overcalling by BD phoenix NMIC-500 panel.

We aimed to assess the accuracy of BD Phoenix for determining carbapenem susceptibility because we observed a decline in carbapenem susceptibility rate from the biannual cumulative data, after we transitioned to the BD Phoenix form Vitek 2 system. Between October 2021 and May 2022, we collected 82 non-duplicated Enterobacterales showing non-susceptible to at least one of the three carbapenems by BD Phoenix. We performed the broth microdilution (BMD) and disk diffusion (DD) according to the CLSI guideline. Compared to BMD, the categorical agreements for ertapenem (ERT), imipenem (IPM) and meropenem (MEPM) was 58.8%, 56.8% and 91.5% for BD Phoenix and it was 85.4%, 89.0%, and 97.6%, respectively, for DD (p value; 0.0001 for ERT and IPM, p value; 0.17 for MEPM). The major errors/minor errors for ERT, IPM, and MEPM were 14.0%/31.7%, 2.94%/40.7%, and 2.56%/6.10%, respectively for BD Phoenix, compared to 0%/14.6%, 0%/9.8%, and 0%/2.5%, for DD. While errors in the BD Phoenix showed tendency towards resistance, those in DD displayed no tendency towards either resistance or susceptibility. With DD, 21 out of the 27 isolates showing susceptible/intermediate/susceptible pattern (ERT/IPM/MEPM) and 13 out of the 16 isolates showing intermediate/susceptible/susceptible pattern (ERT/IPM/MEPM), were correctly categorized by DD. However, for 22 isolates showing resistant/susceptible/susceptible pattern (ERT/IPM/MEPM), only 13 isolates were correctly categorized by DD. In conclusion, to mitigate the risk of overcalling carbapenem non-susceptibility with BD Phoenix, it will be helpful to perform a complementary test using DD and to provide comments on the DD results to clinicians.

Water-soluble phenolics from Phoenix dactylifera fruits as potential reno-protective agent against cisplatin-induced toxicity: pre- and post-treatment strategies.

Nephrotoxicity is the major side effect of cisplatin, an effective platinum-based chemotherapeutic drug that is applicable in the treatment of several solid-tissue cancers. Studies have indicated that certain water-soluble phenolics offer renal protection. Thus, this study investigates the role of pre and post-treatment of rats with water-soluble phenolics from Phoenix dactylifera (PdP) against nephrotoxicity induced by cisplatin. Rats were either orally pretreated or post-treated with 200 mg/kg body weight of PdP before or after exposure to a single therapeutic dose of cisplatin (5 mg/kg body weight) for 7 successive days intraperitoneally. The protective effects of PdP against Cisplatin-induced nephrotoxicity was based on the evaluation of various biochemical and redox biomarkers, together with histopathological examination of kidney tissues. The composition, structural features, and antioxidative influence of PdP were determined based on chromatographic, spectroscopic, and in vitro antioxidative models. Cisplatin single exposure led to a substantial increase in the tested renal function biomarkers (uric acid, creatinine, and urea levels), associated with an increase in malondialdehyde indicating lipid peroxidation and a significant decline (p < 0.05) in reduced glutathione (GSH) levels in the renal tissue when compared with the control group. A marked decline exists in the kidney antioxidant enzymes (catalase, SOD, and GPx). Nevertheless, treatment with PdP significantly suppressed the heightened renal function markers, lipid peroxidation, and oxidative stress. Spectroscopic analysis revealed significant medicinal phenolics, and in vitro tests demonstrated antioxidative properties. Taken together, results from this study indicate that pre- and/or post-treatment strategies of PdP could serve therapeutic purposes in cisplatin-induced renal damage.

Phoenix dactylifera L.: An Overview of Phytochemical Constituents and Impact on Women's Health.

Phoenix dactylifera L. (date palm) is the most significant member of the palm family (Arecaceae), particularly in the Middle East and Arab World. It is a valuable source of both primary and secondary metabolites including sugars, amino acids, phenolic acids, flavonoids, proanthocyanidins, carotenoids, phytosterols, terpenes and sphingolipids, besides vitamins and minerals. Besides, it possesses a wide array of pharmacologic activities viz. immunomodulatory, antioxidant, anti-inflammatory, hepatoprotective, nephroprotective, anti-mutagenic and anti-cancer activities, in addition to its positive effects on male and female fertility. Further research is still required to deeply understand its clinical implications, especially concerning women's health. Moreover, there are other Phoenix species that still need to be investigated to learn more about their undiscovered phytochemical components and biological activities.

Whole mitochondrial and chloroplast genome sequencing of Tunisian date palm cultivars: diversity and evolutionary relationships.

BACKGROUND: Date palm (Phoenix dactylifera L.) is the most widespread crop in arid and semi-arid regions and has great traditional and socioeconomic importance, with its fruit well-known for its high nutritional and health value. However, the genetic variation of date palm cultivars is often neglected. The advent of high-throughput sequencing has made possible the resequencing of whole organelle (mitochondria and chloroplast) genomes to explore the genetic diversity and phylogenetic relationships of cultivated plants with unprecedented detail. RESULTS: Whole organelle genomes of 171 Tunisian accessions (135 females and 36 males) were sequenced. Targeted bioinformatics pipelines were used to identify date palm haplotypes and genome variants, aiming to provide variant annotation and investigate patterns of evolutionary relationship. Our results revealed the existence of unique haplotypes, identified by 45 chloroplastic and 156 mitochondrial SNPs. Estimation of the effect of these SNPs on genes functions was predicted in silico. CONCLUSIONS: The results of this study have important implications, in the light of ongoing environmental changes, for the conservation and sustainable use of the genetic resources of date palm cultivars in Tunisia, where monoculture threatens biodiversity leading to genetic erosion. These data will be useful for breeding and genetic improvement programs of the date palm through selective cross-breeding.

Evaluation of Piperacillin-Tazobactam Testing against Enterobacterales by the Phoenix, MicroScan, and Vitek2 Tests Using Updated Clinical and Laboratory Standards Institute Breakpoints.

In 2022, the Clinical and Laboratory Standards Institute (CLSI) updated piperacillin-tazobactam (TZP) breakpoints for Enterobacterales, based on substantial data suggesting that historical breakpoints did not predict treatment outcomes for TZP. The U.S. Food and Drug Administration (FDA) has not yet adopted these breakpoints, meaning commercial manufacturers of antimicrobial susceptibility testing devices cannot obtain FDA clearance for the revised breakpoints. We evaluated the Phoenix (BD, Sparks, MD), MicroScan (Beckman Coulter, Sacramento, CA), and Vitek2 (bioMérieux, Durham, NC) TZP MICs compared to reference broth microdilution for a collection of 284 Enterobacterales isolates. Phoenix (n = 167 isolates) demonstrated 84.4% categorical agreement (CA), with 4.2% very major errors (VMEs) and 1.8% major errors (MEs) by CLSI breakpoints. In contrast, CA was 85.0% with 4.3% VMEs and 0.8% MEs for the Phoenix with FDA breakpoints. MicroScan (n = 55 isolates) demonstrated 80.0% CA, 36.4% VMEs, and 4.8% MEs by CLSI breakpoints and 81.8% CA, 44.4% VMEs, and 0.0% MEs by FDA breakpoints. Vitek2 (n = 62 isolates) demonstrated 95.2% CA, 6.3% VMEs, and 0.0% MEs by CLSI and 96.8% CA, 0.0% VMEs, and 2.2% MEs by FDA breakpoints. Overall, the performance of the test systems was not substantially different using CLSI breakpoints off-label than using on-label FDA breakpoints. However, limitations were noted with higher-than-desired VME rates (all three systems) and lower-than-desired CA (MicroScan and Phoenix). Laboratories should consider adoption of the revised CLSI breakpoints with automated test systems but be aware that some performance challenges exist for testing TZP on automated systems, regardless of breakpoints applied.

Date palm spathe extract reverses chronic stress-induced changes in dendritic arborization in the amygdala and impairment of hippocampal long-term potentiation.

Chronic restraint stress induces anxiety-like behaviors and emotional abnormalities via an alteration of synaptic remodeling in the amygdala and the hippocampus. Given that the date palm spathe has been shown to have neuroprotective effects on different experimental models, this study aimed to address whether the date palm spathe extract (hydroalcoholic extract of date palm spathe [HEDPP]) can reduce chronic restraint stress-induced behavioral, electrophysiological, and morphological changes in the rat model. Thirty-two male Wistar rats (weight 200-220 g) were randomly divided into control, stress, HEDPP, and stress + HEDPP for 14 days. Animals were submitted to restraint stress for 2 h per day for 14 consecutive days. The animals of the HEDPP and stress + HEDPP groups were supplemented with HEDPP (125 mg/kg) during these 14 days, 30 min before being placed in the restraint stress tube. We used passive avoidance, open-field test, and field potential recording to assess emotional memory, anxiety-like behavioral and long-term potentiation in the CA1 region of the hippocampus, respectively. Moreover, Golgi-Cox staining was used to investigate the amygdala neuron dendritic arborization. Results showed that stress induction was associated with behavioral changes (anxiety-like behavioral and emotional memory impairment), and the administration of HEDPP effectively normalized these deficits. HEDPP remarkably amplified the slope and amplitude of mean-field excitatory postsynaptic potentials (fEPSPs) in the CA1 area of the hippocampus in stressed rats. Chronic restraint stress significantly decreased the dendritic arborization in the central and basolateral nucleus of the amygdala neuron. HEDPP suppressed this stress effect in the central nucleus of the amygdala. Our findings indicated that HEDPP administration improves stress-induced learning impairment and memory and anxiety-like behaviors by preventing adverse effects on synaptic plasticity in the hippocampus and amygdala.

Chemical Profile of the Pits Oil from the Tunisian 'Alig' Cultivar of Phoenix dactylifera L.: In Vivo Wound Healing Potential Evaluation of a Cream Formulated from the Extracted Oil and Insights from Molecular Docking and SAR Analysis.

Since ancient times the oil from date palm pits (Phoenix dactylifera L.) has been used to heal wounds. In order to prove this traditional usage of the pits, this oil was extracted from the pits of the Tunisian cultivar 'Alig' and its physico-chemical properties and the chemical composition were evaluated. The fatty acid profile, evidenced by GC, allowed to classify this oil as an oleic-myristic acid oil with a clear abundance of oleic acid (53.66 %). 1 H and 13 C-NMR as well as FT-IR analyses confirmed the presence of fatty acids in triglyceride forms. Furthermore, in vivo wound healing activity of a cream formulated from the extracted oil was performed, for the first time, using a rat model and was compared to placebo cream and a commercial formulation, MEBO®. This study showed that the test cream promoted the healing of pressure ulcers better than the placebo cream and the MEBO® ointment. The results showed that this vegetable oil is able to improve the healing of infected wounds in rats, thus supporting its traditional use. The contribution of the main oleic, linoleic and myristic acids that can be derived from enzymatic hydrolysis to the healing activity of the whole pits oil was predicted by in silico study and the calculated pharmacokinetics parameters.

Innovation in mental health care: Bertram Mandelbrote, the Phoenix Unit and the therapeutic community approach.

Bertram Mandelbrote was Physician Superintendent and Consultant Psychiatrist at Littlemore Hospital in Oxford from 1959 to 1988. A humane pragmatist rather than theoretician, Mandelbrote was known for his facilitating style of leadership and working across organisational boundaries. He created the Phoenix Unit, an innovative admission unit run on therapeutic community lines which became a hub for community outreach. Material drawn from oral histories and witness seminars reflects the remarkably unstructured style of working on the Phoenix Unit and the enduring influence of Mandelbrote and fellow consultant Benn Pomryn's styles of leadership. Practices initiated at Littlemore led to a number of innovative services in Oxfordshire. These innovations place Mandelbrote as a pioneer in social psychiatry and the therapeutic community approach.

Comparative study of the morphological characteristics of Phoenix dactylifera L. cultivars in Al-Madinah Al-Munawarah-Saudi Arabia.

BACKGROUND: Phoenix dactylifera L. belongs to the subfamily Coryphoideae. Saudi Arabia is the third producing country of dates in the world with over a million tons of dates every year. P. dactylifera is one of the most important species that grows in Al-Madinah and has cultivars that are distinguished by their appearance and taste. RESULTS: This study aimed to investigate the importance of morphology among P. dactylifera cultivars by using statistical analysis and the ability to identify the cultivars just by looking at them in the obvious characters of palms. Plant specimens were collected from different areas in the Al-Madinah region. All the data obtained from morphology were transferred to numerical characters and used in the multivariate statistical package (MVSP) to study the similarity between the cultivars and give phenetic clusters. One-way ANOVA test and the least significant difference test (LSD) were used to find the significant differences among cultivars in p = 0.05. The numerical data that was recorded indicated significant differences among cultivars. Principal coordinates analysis and cluster analysis (UPGMA) were utilized to study the distance of similarities and differences between cultivars. CONCLUSION: The most distinguishing characteristics were fruit and seed, and the least characteristic was the trunk. However, the features of spine, frond and leaflet were also important in distinguishing between cultivars.

Effects of Sporisorium reiliana polysaccharides and Phoenix dactylifera monosaccharides on the gut microbiota and serum metabolism in mice with fructose-induced hyperuricemia.

In recent decades, the prevalence of hyperuricemia has increased, and dietary fructose is an important risk factor for the development of this disease. This study investigated and compared the effects of Sphacelotheca reiliana polysaccharides and Phoenix dactylifera monosaccharides on a series of physiological and biochemical indicators and on the metagenomes and serum metabolites in mice with hyperuricemia caused by a high-fructose diet. S. reiliana polysaccharides inhibited uric acid biosynthesis and promoted uric acid excretion, thereby alleviating the hyperuricemia phenotype. In addition, hyperuricemia was closely related to the gut microbiota. After treatment with S. reiliana polysaccharides, the abundances of Bacteroidetes and Proteobacteria in the mouse intestines were decreased, the expression of genes involved in glycolysis/gluconeogenesis metabolic pathways and purine metabolism was downregulated, and the dysfunction of the gut microbiota was alleviated. With regard to serum metabolism, the abundance of hippuric acid, uridine, kynurenic acid, propionic acid and arachidonoyl decreased, and the abundances of serum metabolites in inflammatory pathways involved in kidney injury and gout, such as bile acid metabolism, purine metabolism and tryptophan metabolism pathways, decreased. P. dactylifera monosaccharides aggravated hyperuricemia. This research provides a valuable reference for the development of sugar applications.

Modelling the inactivation, survival and growth of Salmonella enterica under osmotic stress considering inoculum phase and serotype.

AIMS: This study evaluated the behaviour of the Salmonella enterica serotypes in osmotically stressful BHI broth (0.940 ≤ aw  ≤ 0.960), assessing inoculum from two stages of the bacterial life cycle (exponential and stationary) and two temperatures (25°C and 35°C). METHODS AND RESULTS: Four S. enterica serotypes (Typhimurium, Enteritidis, Heidelberg and Minnesota) were grown in stressful BHI at 25°C. A mathematical model was proposed for describing the total microbial count as the sum of two subpopulations, inactivating and surviving-then-growing. When submitted to aw of 0.950 and 0.960, all strains showed a decreased count, followed by a period of unchanged count and then exponential growth (Phoenix Phenomenon). Strains inoculated at aw  = 0.940 and 0.945 showed inactivation kinetics only. Cells cultivated at 25°C and inoculated from the exponential phase were the most reactive to the osmotic stress, showing a higher initial population reduction and shorter adaptation period. The proposed model described the inactivation data and the Phoenix Phenomenon accurately. CONCLUSIONS: The results quantified the complex response of S. enterica to the osmotic environment in detail, depending on the inoculum characteristic and serotype evaluated. SIGNIFICANCE AND IMPACT OF STUDY: Quantifying these differences is truly relevant to food safety and improves risk analysis.