Placental Mosaicism in Multiple Gestation: Complete Hydatidiform Mole with Coexisting Twin Fetus.

Hydatidiform mole coexistent with a live fetus (CMCF) is a rare entity occurring in 1:20,000 to 1:100,000 pregnancies. Three mechanisms of this type are possible: (1) a singleton pregnancy consisting of partial mole with a triploid fetus, (2) a twin gestation consisting of an androgenic complete hydatidiform mole with a biparental diploid fetus, and (3) a twin gestation consisting of a biparental diploid fetus with a normal placenta and a partial hydatidiform mole (PHM) with a triploid fetus. The abnormal triploid fetus in a partial mole tends to die in the first trimester while the fetus coexisting with a complete or partial mole in the dizygotic twin pregnancy has a chance to survive. Early detection and diagnosis of a molar gestation with a viable fetus is needed to allow medical interventions, if available. Three cases of complete mole with a twin fetus (CMTF) that were diagnosed in the prenatal period by ultrasonography will be presented. This report will also discuss the indications for continuing the pregnancy, and review the literature on the recommended prenatal care, intrapartum management, and postpartum surveillance. This report aims to encourage others to document cases of CMTF in order to arrive at a consensus regarding its optimal management.

Permittivity tensor imaging: modular label-free imaging of 3D dry mass and 3D orientation at high resolution.

The dry mass and the orientation of biomolecules can be imaged without a label by measuring their permittivity tensor (PT), which describes how biomolecules affect the phase and polarization of light. Three-dimensional (3D) imaging of PT has been challenging. We present a label-free computational microscopy technique, PT imaging (PTI), for the 3D measurement of PT. PTI encodes the invisible PT into images using oblique illumination, polarization-sensitive detection and volumetric sampling. PT is decoded from the data with a vectorial imaging model and a multi-channel inverse algorithm, assuming uniaxial symmetry in each voxel. We demonstrate high-resolution imaging of PT of isotropic beads, anisotropic glass targets, mouse brain tissue, infected cells and histology slides. PTI outperforms previous label-free imaging techniques such as vector tomography, ptychography and light-field imaging in resolving the 3D orientation and symmetry of organelles, cells and tissue. We provide open-source software and modular hardware to enable the adoption of the method.

Knowledge and Practice Regarding Abnormal Vaginal Discharge Among Adolescent Females in Riyadh City: An Observational Study.

Introduction Vaginal discharge (VD) is a common condition that affects women during their childbearing years and often requires medical attention. It results from the physiological secretion of cervical and Bartholin's glands, as well as the shedding of vaginal epithelial cells caused by bacterial action in the vagina, which alters the acidic environment of the vagina. Experiencing vaginal symptoms is a common reason for seeking medical attention, especially among women during their reproductive years. This often leads to a visit to an obstetrician or a gynecologist. Accordingly, addressing such issues becomes even more crucial. The aim of this study is to assess the knowledge and practice regarding abnormal VD (AVD) among adolescent females in Riyadh City, Saudi Arabia. Methods The present study utilized a correlational cross-sectional survey methodology conducted in Riyadh City. The questionnaire was employed as the data collection instrument from November 2022 to November 2023. Eligibility for inclusion was limited to adolescent females and students living in Riyadh City, aged from 14 to 20 years. Electronic consent was obtained from participants aged 18 years and above, while consent from guardians was sought for those below 18 years. This sample size was determined with a minimum requirement of 500 participants, and 824 were involved. The questionnaire encompassed several sections, including demographic characteristics (gender, age, education, and menstruation history), history of AVD, knowledge regarding VD, and students' practices and behaviors related to VD. Cronbach's alpha values for all the sections were more than 0.7. Data analysis was performed using statistical software, employing descriptive analysis, chi-square tests, and t-tests. Results A total of 824 girls were included, and their ages ranged from 14 to 20 years, with a mean age of (16 years ± 5) years old. Exactly 697 (84.6%) were high school students. Most of the study students (85.1%; 701) complained of an AVD at any point in their lives. Only 97 (11.8%) of the study students had a good knowledge level of VD. Higher age, marriage, late menarche, and seeking medical care for complaints of VD were the factors associated with a high knowledge level about VD (P<0.05). Additionally, 44.2% of school-age females sought medical care when experiencing AVD, with reasons including worsening symptoms over time and fear of serious diseases. However, a significant portion of participants opted for self-treatment using herbal remedies, medication from pharmacies, or leaving VD untreated, citing reasons such as perceiving it as a simple condition or fearing examination and disclosure. Conclusion In summary, the current study revealed that adolescent females demonstrate a sub-optimal level of knowledge regarding AVD. These findings are primarily observed among adolescent girls and individuals who exhibit a reluctance to seek appropriate medical intervention when having AVD.

Crosstalk involving two-component systems in Staphylococcus aureus signaling networks.

Staphylococcus aureus poses a serious global threat to human health due to its pathogenic nature, adaptation to environmental stress, high virulence, and the prevalence of antimicrobial resistance. The signaling network in S. aureus coordinates and integrates various internal and external inputs and stimuli to adapt and formulate a response to the environment. Two-component systems (TCSs) of S. aureus play a central role in this network where surface-expressed histidine kinases (HKs) receive and relay external signals to their cognate response regulators (RRs). Despite the purported high fidelity of signaling, crosstalk within TCSs, between HK and non-cognate RR, and between TCSs and other systems has been detected widely in bacteria. The examples of crosstalk in S. aureus are very limited, and there needs to be more understanding of its molecular recognition mechanisms, although some crosstalk can be inferred from similar bacterial systems that share structural similarities. Understanding the cellular processes mediated by this crosstalk and how it alters signaling, especially under stress conditions, may help decipher the emergence of antibiotic resistance. This review highlights examples of signaling crosstalk in bacteria in general and S. aureus in particular, as well as the effect of TCS mutations on signaling and crosstalk.

Clinical features of neurotoxicity after CD19 CAR T-cell therapy in mantle cell lymphoma.

ABSTRACT: CD19 chimeric antigen receptor (CAR) T-cell therapy has proven highly effective for treating relapsed/refractory mantle cell lymphoma (MCL). However, immune effector cell-associated neurotoxicity syndrome (ICANS) remains a significant concern. This study aimed to evaluate the clinical, radiological, and laboratory correlatives associated with ICANS development after CD19 CAR T-cell therapy in patients with MCL. All patients (N = 26) who received standard-of-care brexucabtagene autoleucel until July 2022 at our institution were evaluated. Laboratory and radiographic correlatives including brain magnetic resonance imaging (MRI) and electroencephalogram (EEG) were evaluated to determine the clinical impact of ICANS. Seventeen (65%) patients experienced ICANS after treatment, with a median onset on day 6. Ten (38%) patients experienced severe (grade ≥3) ICANS. All patients with ICANS had antecedent cytokine release syndrome (CRS), but no correlation was observed between ICANS severity and CRS grade. Overall, 92% of EEGs revealed interictal changes; no patients experienced frank seizures because of ICANS. In total, 86% of patients with severe ICANS with postinfusion brain MRIs demonstrated acute neuroimaging findings not seen on pretreatment MRI. Severe ICANS was also associated with higher rates of cytopenia, coagulopathy, increased cumulative steroid exposure, and prolonged hospitalization. However, severe ICANS did not affect treatment outcomes of patients with MCL. Severe ICANS is frequently associated with a range of postinfusion brain MRI changes and abnormal EEG findings. Longer hospitalization was observed in patients with severe ICANS, especially those with abnormal acute MRI or EEG findings, but there was no discernible impact on overall treatment response and survival.

Prevalence, Demographic, and Clinical Factors Associated With Cognitive Dysfunction in Patients With Neuromyelitis Optica Spectrum Disorder.

BACKGROUND AND OBJECTIVES: Neuromyelitis optica spectrum disorder (NMOSD) is a chronic CNS demyelinating autoimmune disorder targeting the astrocyte antigen aquaporin-4 (AQP4), typically presenting with optic neuritis, transverse myelitis, and brain syndromes. Cognitive dysfunction (CD) in NMOSD is under-recognized and poorly understood. The purpose of this study was to evaluate the prevalence and clinical variables associated with CD in NMOSD. METHODS: This observational retrospective study with longitudinal follow-up describes a clinical cohort seen in the Collaborative International Research in Clinical and Longitudinal Experience Study in NMOSD. Serial Montreal Cognitive Assessments (MoCAs) were performed upon enrollment and at 6-month intervals to evaluate longitudinal cognitive function relative to demographic and disease-related factors. We used 2-tailed t test, analysis of variance, the χ2 test, linear regression for univariable and adjusted analyses and simultaneous linear regression and mixed-effects model for multivariable analyses. RESULTS: Thirty-four percent (75/219) of patients met criteria for CD (MoCA <26); 29% (64/219) showed mild dysfunction (MoCA 20-26/30), and 5% (11/219) showed moderate (MoCA <20/30) dysfunction. Patients with less neurologic disability and lower pain scores had higher MoCA scores (95% CI 0.24-0.65 and 95% CI 0.09-0.42, respectively). Patients with at least high school education scored higher on the MoCA (95% CI 2.2-5). When comparing patients dichotomized for CD, patients never on rituximab scored higher than patients only treated with rituximab (p < 0.029). There was no significant association between annualized relapse rate, age, sex, disease duration, AQP4 serostatus or brain lesions, and CD. CD was more pronounced among Black than White patients (95% CI -2.7 to -0.7). Multivariable analysis of serial MoCA did not indicate change (p = 0.715). Descriptive analysis of serial MoCA showed 30% (45/150) of patients with worsening MoCA performance had impaired language and verbal recall. DISCUSSION: To our knowledge, this is the largest study of diverse cohort to investigate CD in patients with NMOSD. Our findings demonstrate 34% of patients with NMOSD experience mild-to-moderate CD, while 30% of patients demonstrated decline on serial testing. The substantial prevalence of CD in this pilot report highlights the need for improved and validated screening tools and comprehensive measures to investigate CD in NMOSD.

Camptothecin structure simplification elaborated new imidazo[2,1-b]quinazoline derivative as a human topoisomerase I inhibitor with efficacy against bone cancer cells and colon adenocarcinoma.

Camptothecin is a pentacyclic natural alkaloid that inhibits the hTop1 enzyme involved in DNA transcription and cancer cell growth. Camptothecin structure pitfalls prompted us to design new congeners using a structure simplification strategy to reduce the ring extension number from pentacyclic to tetracyclic while maintaining potential stacking of the new compounds with the DNA base pairs at the Top1-mediated cleavage complex and aqueous solubility, as well as minimizing compound-liver toxicity. The principal axis of this study was the verification of hTop1 inhibiting activity as a possible mechanism of action and the elaboration of new simplified inhibitors with improved pharmacodynamic and pharmacokinetic profiling using three structure panels (A-C) of (isoquinolinoimidazoquinazoline), (imidazoquinazoline), and (imidazoisoquinoline), respectively. DNA relaxation assay identified five compounds as hTop1 inhibitors belonging to the imidazoisoquinolines 3a,b, the imidazoquinazolines 12, and the isoquinolinoimidazoquinazolines 7a,b. In an MTT cytotoxicity assay against different cancer cell lines, compound 12 was the most potent against HOS bone cancer cells (IC50 = 1.47 µM). At the same time, the other inhibitors had no detectable activity against any cancer cell type. Compound (12) demonstrated great penetrating power in the HOS cancer cells' 3D-multicellular tumor spheroid model. Bioinformatics research of the hTop1 gene revealed that the TP53 cell proliferative gene is in the network of hTop1. The finding is confirmed empirically using the gene expression assay that proved the increase in p53 expression. The impact of structure simplification on compound 12 profile, characterized by the absence of acute oral liver toxicity when compared to Doxorubicin as a standard inhibitor, the lethal dose measured on Swiss Albino female mice and reported at LD50 = 250 mg/kg, and therapeutic significance in reducing colon adenocarcinoma tumor volume by 75.36 % after five weeks of treatment with compound 12. The molecular docking solutions of the active CPT-based derivative 12 and the inactive congener 14 into the active site of hTop1 and the activity cliffing of such MMP directed us to recommend the addition of HBD and HBA variables to compound 12 imidazoquinazoline core scaffold to enhance the potency via hydrogen bond formation with the major groove amino acids (Asp533, Lys532) as well as maintaining the hydrogen bond with the minor groove amino acid Arg364.

A scoping review of artificial intelligence within pharmacy education.

OBJECTIVES: This scoping review aimed to summarize the available literature on the use of artificial intelligence (AI) in pharmacy education and identify gaps where additional research is needed. FINDINGS: Seven studies specifically addressing the use of AI in pharmacy education were identified. Of these 7 studies, 5 focused on AI use in the context of teaching and learning, 1 on the prediction of academic performance for admissions, and the final study focused on using AI text generation to elucidate the benefits and limitations of ChatGPT use in pharmacy education. SUMMARY: There are currently a limited number of available publications that describe AI use in pharmacy education. Several challenges exist regarding the use of AI in pharmacy education, including the need for faculty expertise and time, limited generalizability of tools, limited outcomes data, and several legal and ethical concerns. As AI use increases and implementation becomes more standardized, opportunities will be created for the inclusion of AI in pharmacy education.

Women's Knowledge, Attitudes, and Practice About Female Genital Cosmetic Surgery: A Cross-Sectional Study in Saudi Arabia.

Introduction Vulvoplasty, or female genital cosmetic surgery (FGCS), refers to any surgical alteration of the vaginal or labial anatomy for aesthetic or medical reasons. It aims to restore or enhance the female genitals and can involve multiple procedures such as labiaplasty, clitoral unhooding, monsplasty, vaginoplasty, hymenoplasty, G-spot augmentation, frenuloplasty, perineoplasty, fat injections, or a combination of these. Labiaplasty is currently the most popular procedure among patients. Since the public is exploring FGCS benefits in the media, it can be foreseen that it will soon gain popularity among the population of Saudi Arabia. As a result, the purpose of this study is to assess women's attitudes and knowledge towards genital cosmetic surgeries in Saudi Arabia.  Methods This correlational cross-sectional survey was conducted in Saudi Arabia among women aged 18 years and above, using an online self-structured questionnaire distributed from April 2023 to October 2023. The sample size of 594 respondents was determined based on a minimum requirement of 500 participants, with a confidence level of 95% and a study power of 95%. A convenient sampling method was employed to select participants, and data collection was carried out through a self-administered online questionnaire distributed via various social media platforms. The survey was self-structured, and Cronbach's alpha values for all sections were greater than 0.7. These sections include demographic characteristics, sexual life and obstetric history, and women's knowledge, practices, and attitudes toward FGCS. Descriptive analysis, chi-square test, and t-test were used for data analysis using SPSS software.  Results A total of 589 eligible women were included in the study; 284 (48.2%) were from the central region, and ages ranged from 18 to 65 years, with a mean age of 33.5 years. A total of 401 (68.1%) were married, 366 (62.1%) had a bachelor degree. Two hundred and ninety-one (49.4%) participants heard about FGCS, 165 (28%) knew that it involves surgical procedures to change the appearance of the female genitalia, 144 (24.4%) said it is also known as vaginal rejuvenation or designer vagina surgery and 200 (34%) knew it can involve procedures such as labiaplasty, clitoral hood reduction, or vaginal tightening, while 190 (32.3%) reported it is sometimes done for aesthetic reasons but may also be done for medical reasons. Only 45 (7.6%) had undergone FGCS, but 112 (19%) confirmed they consider undergoing FGCS for themselves. Four hundred and ninety-eight (84.6%) participants thought that it's important to have access to support services, such as counseling or peer support, 471 (80%) expressed that it's important that healthcare providers in Saudi Arabia are knowledgeable about FGCS, 425 (72.2%) were concerned about the potential risks and complications of FGCS. Conclusion In conclusion, the current study revealed that nearly one out of five women were knowledgeable about FGCS, mainly about the nature and types of the procedure. Higher knowledge levels about FGCS were associated with younger age, higher educational levels, and women who were more likely to consider undergoing FGCS in the future.

Pharmacy students' perceptions and attitudes toward face-to-face vs. virtual team-based learning (TBL) in the didactic curriculum: A mixed-methods study.

INTRODUCTION: Virtual TBL is an online adaptation of the team-based learning (TBL) instructional strategy, emphasizing collaborative learning and problem-solving. The emergency shift to virtual TBL during the COVID-19 pandemic presented unique challenges. This study aims to 1) compare overall pharmacy students' perceptions and attitudes toward face-to-face (FTF) TBL vs. virtual TBL in the didactic curriculum and stratify their perceptions and attitudes by various students' characteristics; 2) evaluate students' perceptions of the strengths and weaknesses of virtual TBL. METHODS: This mixed-methods, pre-post, cross-sectional study utilized an anonymous survey to collect the data. Pharmacy students completed a survey to compare their perceptions and attitudes toward learning, class experience, learning outcomes achieved, and satisfaction with FTF TBL vs. virtual TBL using a 5-point Likert-type scale. Additionally, the survey included two open-ended questions to gather students' perceptions of the strengths and weaknesses of virtual TBL. Quantitative survey data were analyzed using the Wilcoxon matched-pairs signed rank exact test, while qualitative survey data were analyzed using thematic analysis. RESULTS: A total of 117 students (response rate of 59.4%) completed the study survey. Pharmacy students perceived FTF TBL to be superior to virtual TBL in their attitudes toward learning, class experience, learning outcomes achieved, and overall satisfaction across various students' characteristics. While the students identified some unique strengths of using virtual TBL, they also highlighted several weaknesses of using this learning modality compared to FTF TBL. CONCLUSIONS: Pharmacy students perceived FTF TBL to be superior to virtual TBL across various students' characteristics. These findings can be helpful to pharmacy programs considering the implementation of virtual TBL in their didactic curricula. Future research should explore whether a purposefully designed virtual TBL environment, as opposed to the pandemic-driven emergency TBL planning, can influence students' perceptions and attitudes toward virtual TBL.

A FOXC2 inhibitor, MC-1-F2, as a therapeutic candidate for targeting EMT in castration-resistant prostate cancer.

Androgen deprivation therapy (ADT) is the major treatment option for advanced prostate cancer. However, prostate cancer can develop into androgen-independent castration-resistant prostate cancer (CRPC) which is resistant to ADT. An alternative treatment strategy for CRPC can be targeting the epithelial-mesenchymal transition (EMT). EMT is governed by a series of transcription factors of which forkhead box protein C2 (FOXC2) is a central mediator. Our previous research into the inhibition of FOXC2 in breast cancer cells lead to the discovery of MC-1-F2, the first direct inhibitor of FOXC2. In current study on CRPC, MC-1-F2 has shown a decrease in mesenchymal markers, inhibition of cancer stem cell (CSC) properties and decrease in invasive capabilities of CRPC cell lines. We have also demonstrated a synergistic effect between MC-1-F2 and docetaxel treatments, leading to a decrease in docetaxel dosage, suggesting the possible combination therapy of MC-1-F2 and docetaxel for the effective treatment of CRPC.

NH125 Sensitizes Staphylococcus aureus to Cell Wall-Targeting Antibiotics through the Inhibition of the VraS Sensor Histidine Kinase.

Staphylococcus aureus utilizes the two-component regulatory system VraSR to receive and relay environmental stress signals, and it is implicated in the development of bacterial resistance to several antibiotics through the upregulation of cell wall synthesis. VraS inhibition was shown to extend or restore the efficacy of several clinically used antibiotics. In this work, we study the enzymatic activity of the VraS intracellular domain (GST-VraS) to determine the kinetic parameters of the ATPase reaction and characterize the inhibition of NH125 under in vitro and microbiological settings. The rate of the autophosphorylation reaction was determined at different GST-VraS concentrations (0.95 to 9.49 µM) and temperatures (22 to 40°C) as well as in the presence of different divalent cations. The activity and inhibition by NH125, which is a known kinase inhibitor, were assessed in the presence and absence of the binding partner, VraR. The effects of inhibition on the bacterial growth kinetics and gene expression levels were determined. The GST-VraS rate of autophosphorylation increases with temperature and with the addition of VraR, with magnesium being the preferred divalent cation for the metal-ATP substrate complex. The mechanism of inhibition of NH125 was noncompetitive in nature and was attenuated in the presence of VraR. The addition of NH125 in the presence of sublethal doses of the cell wall-targeting antibiotics carbenicillin and vancomycin led to the complete abrogation of Staphylococcus aureus Newman strain growth and significantly decreased the gene expression levels of pbpB, blaZ, and vraSR in the presence of the antibiotics. IMPORTANCE This work characterizes the activity and inhibition of VraS, which is a key histidine kinase in a bacterial two-component system that is involved in Staphylococcus aureus antibiotic resistance. The results show the effect of temperature, divalent ions, and VraR on the activity and the kinetic parameters of ATP binding. The value of the KM of ATP is vital in designing screening assays to discover potent and effective VraS inhibitors with high translational potential. We report the ability of NH125 to inhibit VraS in vitro in a noncompetitive manner and investigate its effect on gene expression and bacterial growth kinetics in the presence and absence of cell wall-targeting antibiotics. NH125 effectively potentiated the effects of the antibiotics on bacterial growth and altered the expression of the genes that are regulated by VraS and are involved in mounting a resistance to antibiotics.

Visualizing Sphingosine-1-Phosphate Receptor 1(S1P1) Signaling During Central Nervous System De- and Remyelination.

Multiple sclerosis (MS) is an inflammatory-demyelinating disease of the central nervous system (CNS) mediated by aberrant auto-reactive immune responses. The current immune-modulatory therapies are unable to protect and repair immune-mediated neural tissue damage. One of the therapeutic targets in MS is the sphingosine-1-phosphate (S1P) pathway which signals via sphingosine-1-phosphate receptors 1-5 (S1P1-5). S1P receptors are expressed predominantly on immune and CNS cells. Considering the potential neuroprotective properties of S1P signaling, we utilized S1P1-GFP (Green fluorescent protein) reporter mice in the cuprizone-induced demyelination model to investigate in vivo S1P - S1P1 signaling in the CNS. We observed S1P1 signaling in a subset of neural stem cells in the subventricular zone (SVZ) during demyelination. During remyelination, S1P1 signaling is expressed in oligodendrocyte progenitor cells in the SVZ and mature oligodendrocytes in the medial corpus callosum (MCC). In the cuprizone model, we did not observe S1P1 signaling in neurons and astrocytes. We also observed ß-arrestin-dependent S1P1 signaling in lymphocytes during demyelination and CNS inflammation. Our findings reveal ß-arrestin-dependent S1P1 signaling in oligodendrocyte lineage cells implying a role of S1P1 signaling in remyelination.

Regulation of T-independent B-cell responses by microRNA-146a.

The microRNA, miR-146a, is a negative feedback regulator of the central immune transcription factor, nuclear factor kappa B (NFkB). MiR-146a plays important roles in the immune system, and miR-146a deficient mice show a complex phenotype with features of chronic inflammation and autoimmune disease. In this study, we examined the role of miR-146a in extrafollicular B-cell responses, finding that miR-146a suppresses cellular responses in vivo and in vitro. Gene expression profiling revealed that miR-146a-deficient B-cells showed upregulation of interferon pathway genes, including Traf6, a known miR-146a target. We next interrogated the role of TRAF6 in these B-cell responses, finding that TRAF6 is required for proliferation by genetic and pharmacologic inhibition. Together, our findings demonstrate a novel role for miR-146a and TRAF6 in the extrafollicular B-cell responses, which have recently been tied to autoimmune disease pathogenesis. Our work highlights the pathogenetic role of miR-146a and the potential of pharmacologic inhibition of TRAF6 in autoimmune diseases in which miR-146a is deregulated.

Immune cell subset profiling in multiple sclerosis after fingolimod initiation and continued treatment: The FLUENT study.

Background: Fingolimod is a sphingosine 1-phosphate receptor modulator approved for relapsing MS. Long-term effects on the immunological profile are not fully understood. Objective: Investigate fingolimod's temporal effects on immune cell subsets, and safety outcomes. Methods: In FLUENT, a 12-month, prospective, non-randomized, open-label, phase IV study, adult participants received fingolimod 0.5 mg/day. Changes in immune cell subsets, anti-John Cunningham virus (JCV) antibody index, and serum neurofilament levels were assessed. Results: 165 fingolimod-naive and 217 participants treated for 2-12 years in routine clinical practice were enrolled. Levels of all monitored peripheral lymphocyte subsets were reduced from month 3 in fingolimod-naive participants. Greatest reductions occurred in naive and central memory CD4+ and CD8+ T cells, and in naive and memory B cells. Most lymphocyte subset levels remained stable in the continuous fingolimod group. Components of the innate immune system remained within reference ranges. No increase in JCV seropositivity was observed. No single cellular subset correlated with anti-JCV antibody index at any time point. Neurofilament levels remained within healthy adult reference limits throughout. No opportunistic infections were reported; no new or unexpected safety signals were observed. Conclusion: FLUENT provides insights into the utility of immunological profiling to evaluate therapy response and potential infection risk.

Nutrition and functional status among Palestinian cancer patients receiving chemotherapy.

Objectives: This study aims to determine the prevalence of malnutrition among cancer patients and to assess the nutritional and functional status of cancer patients undergoing chemotherapy at the Oncology unit of Beit Jala Governmental Hospital in Palestine. Methods: During the data collection period, all patients who received chemotherapy at the hospital's chemotherapy unit were included in this cross-sectional analysis. Anthropometric measurements and biochemical data from the patients' files were used to determine nutritional status. The Nutrition Risk Screening (NRS) 2002 was used to assess the risk of malnutrition. The Functional Assessment of Anorexia/Cachexia Therapy (FAACT) was used to determine functional status. A three-day diet recall was used to determine dietary intake. Results: A total of 153 patients were included in the final analysis. The results revealed that 23.8% of the patients were at risk of malnutrition. Those who were not at risk of malnutrition had a marginally improved functional position. Furthermore, patients aged ≥65 years, males, smokers or former smokers, and those with four or more comorbidities had a significantly higher prevalence of malnutrition. In the logistic model, age >60 years was the only indicator of malnutrition. Conclusion: Malnutrition has a considerable prevalence in the study sample. However, the functional status of patients who were not at risk of malnutrition was marginally better than that of those with malnutrition risk.

Comparative expression of soluble, active human kinases in specialized bacterial strains.

Kinases act as molecular switches for cellular functions and are involved in multiple human pathogeneses, most notably cancer. There is a continuous need for soluble and active kinases for in-vitro drug discovery and structural biology purposes. Kinases remain challenging to express using Escherichia coli, the most widely utilized host for heterologous expression. In this work, four bacterial strains, BL21 (DE3), BL21 (DE3) pLysS, Rosetta, and Arctic Express, were chosen for parallel expression trials along with BL21 (DE3) complemented with folding chaperones DnaJ/K and GroEL/ES to compare their performance in producing soluble and active human kinases. Three representative diverse kinases were studied, Epidermal Growth Factor Receptor kinase domain, Aurora Kinase A kinase domain, and Mitogen-activated protein Kinase Kinase. The genes encoding the kinases were subcloned into pET15b bacterial plasmid and transformed into the bacterial strains. Soluble kinase expression was tested using different IPTG concentrations (1-0.05 mM) at varying temperatures (37°C- 10°C) and induction times (3-24 hours). The optimum conditions for each kinase in all strains were then used for 1L large scale cultures from which each kinase was purified to compare yield, purity, oligomerization status, and activity. Although using specialized strains achieved improvements in yield and/or activity for the three kinases, none of the tested strains was universally superior, highlighting the individuality in kinase expression.

Pericytes regulate vascular immune homeostasis in the CNS.

Pericytes regulate the development of organ-specific characteristics of the brain vasculature such as the blood-brain barrier (BBB) and astrocytic end-feet. Whether pericytes are involved in the control of leukocyte trafficking in the adult central nervous system (CNS), a process tightly regulated by CNS vasculature, remains elusive. Using adult pericyte-deficient mice (Pdgfbret/ret ), we show that pericytes limit leukocyte infiltration into the CNS during homeostasis and autoimmune neuroinflammation. The permissiveness of the vasculature toward leukocyte trafficking in Pdgfbret/ret mice inversely correlates with vessel pericyte coverage. Upon induction of experimental autoimmune encephalomyelitis (EAE), pericyte-deficient mice die of severe atypical EAE, which can be reversed with fingolimod, indicating that the mortality is due to the massive influx of immune cells into the brain. Additionally, administration of anti-VCAM-1 and anti-ICAM-1 antibodies reduces leukocyte infiltration and diminishes the severity of atypical EAE symptoms of Pdgfbret/ret mice, indicating that the proinflammatory endothelium due to absence of pericytes facilitates exaggerated neuroinflammation. Furthermore, we show that the presence of myelin peptide-specific peripheral T cells in Pdgfbret/ret ;2D2tg mice leads to the development of spontaneous neurological symptoms paralleled by the massive influx of leukocytes into the brain. These findings indicate that intrinsic changes within brain vasculature can promote the development of a neuroinflammatory disorder.

Lyophilized growth factor intralesional injection in female pattern hair loss: A clinical and trichoscopic study.

Various therapeutic modalities have been tried for female pattern hair loss (FPHL) treatment. To our knowledge, no previous studies had evaluated the therapeutic effect of lyophilized growth factor (L-GF) intralesional injection in FPHL. The current study aimed to evaluate the efficacy and safety of intralesional L-GF injection in FPHL by clinical and trichoscopic evaluation. This study included 20 patients with FPHL. All patients received three treatment sessions of intralesional injection of L-GF 4 weeks apart. Patients were followed-up for further 3 months. The outcome was evaluated by trichoscopy, photography score, patient's satisfaction score and side effects were reported. Trichoscopic evaluation showed significant posttreatment increase in all hair parameters associated with a significant decrease in vellus hair count. Ludwig's grade II showed posttreatment significant differences in all trichoscopic parameters from the baseline. No significant differences were detected regarding all trichoscopic parameters between the two Ludwig's grades posttreatment. 80% of patients showed photography score improvement that was significantly higher in Ludwig's grade II than in grade I. 100% of patients showed improvement in patient's satisfaction score with insignificant difference between Ludwig's grades. Intralesional injection of L-GF is safe and improved various trichoscopic hair parameters and clinical scores in FPHL.