The Influence of Prenatal Exposure to Methamphetamine on the Development of Dopaminergic Neurons in the Ventral Midbrain.

Methamphetamine, a highly addictive central nervous system (CNS) stimulant, is used worldwide as an anorexiant and attention enhancer. Methamphetamine use during pregnancy, even at therapeutic doses, may harm fetal development. Here, we examined whether exposure to methamphetamine affects the morphogenesis and diversity of ventral midbrain dopaminergic neurons (VMDNs). The effects of methamphetamine on morphogenesis, viability, the release of mediator chemicals (such as ATP), and the expression of genes involved in neurogenesis were evaluated using VMDNs isolated from the embryos of timed-mated mice on embryonic day 12.5. We demonstrated that methamphetamine (10 µM; equivalent to its therapeutic dose) did not affect the viability and morphogenesis of VMDNs, but it reduced the ATP release negligibly. It significantly downregulated Lmx1a, En1, Pitx3, Th, Chl1, Dat, and Drd1 but did not affect Nurr1 or Bdnf expression. Our results illustrate that methamphetamine could impair VMDN differentiation by altering the expression of important neurogenesis-related genes. Overall, this study suggests that methamphetamine use may impair VMDNs in the fetus if taken during pregnancy. Therefore, it is essential to exercise strict caution for its use in expectant mothers.

Can Language Influence Health Decisions? The Role of Foreign Language and Grammatical Structure.

The language used to present an argument has long been argued to influence people's reaction to that argument. This study examined how language and grammatical structure influenced response to health-related dilemmas. We investigated whether medical students' willingness to receive a medical treatment or to take an action (regarding advancing one's own health or other people's health) was influenced by the language (first versus foreign) and the grammatical structures (modifiers and quantifiers) used. Saudi medical students (N = 368) read health-related dilemmas using different adverbial modifiers and quantifiers in Arabic or in English. The participants were randomly assigned to one of four conditions: Arabic with high certainty (i.e., very-modifier and all-quantifier), Arabic with low certainty (no very-modifier and some-quantifier), English with high certainty, and English with low certainty. The results showed that the participants were susceptible to a foreign language effect, but not to a grammatical structure effect. We discuss the implications of these results in relation to how different health-scenarios may affect decision making for health professionals.

The Influence of Prenatal Exposure to Quetiapine Fumarate on the Development of Dopaminergic Neurons in the Ventral Midbrain of Mouse Embryos.

The effects of second-generation antipsychotics on prenatal neurodevelopment, apoptotic neurodegeneration, and postnatal developmental delays have been poorly investigated. Even at standard doses, the use of quetiapine fumarate (QEPF) in pregnant women might be detrimental to fetal development. We used primary mouse embryonic neurons to evaluate the disruption of morphogenesis and differentiation of ventral midbrain (VM) neurons after exposure to QEPF. The dopaminergic VM neurons were deliberately targeted due to their roles in cognition, motor activity, and behavior. The results revealed that exposure to QEPF during early brain development decreased the effects of the dopaminergic lineage-related genes Tyrosine hydroxylase(Th), Dopamine receptor D1 (Drd1), Dopamine transporter (Dat), LIM homeobox transcription factor 1 alfa (Lmx1a), and Cell adhesion molecule L1 (Chl1), and the senescent dopaminergic gene Pituitary homeobox 3 (Pitx3). In contrast, Brain derived neurotrophic factor (Bdnf) and Nuclear receptor-related 1 (Nurr1) expressions were significantly upregulated. Interestingly, QEPF had variable effects on the development of non-dopaminergic neurons in VM. An optimal dose of QEPF (10 µM) was found to insignificantly affect the viability of neurons isolated from the VM. It also instigated a non-significant reduction in adenosine triphosphate formation in these neuronal populations. Exposure to QEPF during the early stages of brain development could also hinder the formation of VM and their structural phenotypes. These findings could aid therapeutic decision-making when prescribing 2nd generation antipsychotics in pregnant populations.

Eco-Friendly, Simple, Fast, and Sensitive UPLC-MS/MS Method for Determination of Pexidartinib in Plasma and Its Application to Metabolic Stability.

Pexidartinib is the first drug approved by the U.S. Food and Drug Administration specifically to treat the rare joint tumor tenosynovial giant cell tumor. In the current study, a validated, selective, and sensitive UPLC-MS/MS assay was developed for the quantitative determination of pexidartinib in plasma samples using gifitinib as an internal standard (IS). Pexidartinib and IS were extracted by liquid-liquid extraction using methyl tert-butyl ether and separated on an acquity BEH C18 column kept at 40 °C using a mobile phase of 0.1% formic acid in acetonitrile: 0.1% formic acid in de-ionized water (70:30). The flow rate was 0.25 mL/min. Multiple reaction monitoring (MRM) was operated in electrospray (ESI)-positive mode at the ion transition of 418.06 > 165.0 for the analyte and 447.09 > 128.0 for the IS. FDA guidance for bioanalytical method validation was followed in method validation. The linearity of the established UPLC-MS/MS assay ranged from 0.5 to 1000 ng/mL with r > 0.999 with a limit of quantitation of 0.5 ng/mL. Moreover, the metabolic stability of pexidartinib in liver microsomes was estimated.

Pharmacy education in Saudi Arabia: Achievements and challenges during the last two decades with a focus on Taif University as a case study.

Basic expectation from graduates of any pharmacy program is to be able to provide pharmaceutical care at both patients and community levels, be able to solve problems arising during practice, be able to improve quality and outcomes of the services provided continuously and be able to respond effectively to patients and community changing needs. Pharmacy education in Saudi Arabia established in 1959 by founding the first college in Riyadh (King Saud University) followed by establishing two pharmacy colleges in Jeddah (King Abdulaziz University, 2001) and Abha (King Khalid University, 2001), then a college in Al Ahsa (King Faisal University, 2002), followed by four colleges three-years later in each of Buraydah (Qassim University, 2005), Madinah (Taibah University, 2005), Taif (Taif University, 2005) and Makkah (Umm Al-Qura University, 2005). Up to date the number of pharmacy colleges offering basic degrees in pharmacy are 21 governmental and eight privates. This review describes pharmacy education in Saudi Arabia, the historical perspective, current situation, and the important features. The report focuses on the changes during the last two decades covering three main aspects (1) Clinical education and training, (2) Research output, and (3) Quality and accreditation.

Description of pharmacists' reported interventions to prevent prescribing errors among in hospital inpatients: a cross sectional retrospective study.

BACKGROUND: Prescribing errors (PEs) are a common cause of morbidity and mortality, both in community practice and in hospitals. Pharmacists have an essential role in minimizing and preventing PEs, thus, there is a need to document the nature of pharmacists' interventions to prevent PEs. The purpose of this study was to describe reported interventions conducted by pharmacists to prevent or minimize PEs in a tertiary care hospital. METHODS: A retrospective analysis of the electronic medical records data was conducted to identify pharmacists' interventions related to reported PEs. The PE-related data was extracted for a period of six-month (April to September 2017) and comprised of patient demographics, medication-related information, and the different interventions conducted by the pharmacists. The study was carried in a tertiary care hospital in Riyadh region. The study was ethically reviewed and approved by the hospital IRB committee. Descriptive analyses were appropriately conducted using the IBM SPSS Statistics. RESULTS: A total of 2,564 pharmacists' interventions related to PEs were recorded. These interventions were reported in 1,565 patients. Wrong dose (54.3 %) and unauthorized prescription (21.9 %) were the most commonly encountered PEs. Anti-infectives for systemic use (49.2 %) and alimentary tract and metabolism medications (18.2 %) were the most common classes involved with PEs. The most commonly reported pharmacists' interventions were dose adjustments (44.0 %), restricted medication approvals (21.9 %), and therapeutic duplications (11 %). CONCLUSIONS: In this study, PEs occurred commonly and pharmacists' interventions were critical in preventing possible medication related harm to patients. Care coordination and prioritizing patient safety through quality improvement initiatives at all levels of the health care system can play a key role in this quality improvement drive. Future studies should evaluate the impact of pharmacists' interventions on patient outcomes.

Eco-Friendly UPLC-MS/MS Method for Determination of a Fostamatinib Metabolite, Tamatinib, in Plasma: Pharmacokinetic Application in Rats.

Fostamatinib is a prodrug of the active metabolite tamatinib, which is a spleen tyrosine kinase (Syk) inhibitor used in the treatment of primary chronic adult immune thrombocytopenia and rheumatoid arthritis. A highly sensitive, rapid, reliable, and green method was developed and validated using ultra-performance liquid chromatography and tandem mass spectrometry (UPLC-MS/MS) for quantification of tamatinib in rat plasma. Ibrutinib was used as internal standard and liquid-liquid extraction was applied using tert-butyl methyl ether. The analyte was separated on an AcquityTM CSH C18 (2.1 mm × 100 mm, 1.7 µm) column using mobile phase consisting of 10 mM ammonium acetate and acetonitrile (10:90) and the flow rate was 0.25 mL/min. Electrospray ionization (ESI) was carried out in positive mode. Quantitation of tamatinib and the IS was performed using multiple reaction monitoring mode with precursor-to-product transitions of m/z 471.1 > 122.0 and m/z 441.1 > 84.0, respectively. The calibration range was 0.1-1000.0 ng/mL and the linearity of the method was ≥0.997. The developed method greenness was investigated. All principal parameters for the method, including linearity, accuracy, precision, recovery, and stability, were within acceptable ranges. Tamatinib pharmacokinetic study in rats was successfully carried out using the developed method.

Orthopedic Surgeons' Views of Hyaluronic Acid Formulations in the Management of Knee Osteoarthritis: A Questionnaire-Based Cross-Sectional Study.

Background and Objectives: Multiple hyaluronic acid (HA) products were approved and marketed to manage osteoarthritis (OA). Although these products are widely prescribed by orthopedic surgeons to manage OA, especially knee OA, the therapeutic value of these products is highly uncertain. Few studies with significant limitations in their designs have indicated positive outcomes among OA patients treated with HA; however, their results were inconclusive. Thus, we aimed to explore the therapeutic value of different HA products in alleviating knee OA pain and improving patients' physical function from the orthopedic surgeons' perspective. Materials and Methods: This was a questionnaire-based cross-sectional study in which practicing orthopedic surgeons in two countries (e.g., Saudi Arabia and Jordan) were invited to participate. The 10-item, newly developed questionnaire inquired about the respondents' sociodemographic characteristics (e.g., age, gender, country, years of experience), and their opinions regarding the efficacy of HA products in the management of OA (e.g., efficacy in improving mobility and alleviating pain). Results: Out of the 200 orthopedic surgeons who were invited to participate, 122 (61%) filled out the questionnaire. Most of the respondents were from Saudi Arabia (58%), aged 35 to 55 years (68%), had at least 10 years of experience (69%), and male (98%). About 80% of the respondents reported prescribing HA, such as Hyalgan®, Orthovisc®, Hyalubrix®, and Crespine Gel®. About 66% of the respondents believed that HA was moderately to highly effective in managing knee OA, and 34% believed that HA was either ineffective or mildly effective. Pain at the site of injection (44.3%) and rash or local skin reactions (22.1%) were the most commonly reported adverse events. Conclusions: The variations in the formulation of different HA brands (e.g., molecular weight and cross-linking) did not seem to offer any therapeutic advantage. HA might have value in the management of knee OA; however, its value is highly uncertain and necessitates more well-designed studies to further examine its therapeutic value.

A Hydrophilic Interaction Liquid Chromatography-Tandem Mass Spectrometry Quantitative Method for Determination of Baricitinib in Plasma, and Its Application in a Pharmacokinetic Study in Rats.

Baricitinib, is a selective and reversible Janus kinase inhibitor, is commonly used to treat adult patients with moderately to severely active rheumatoid arthritis (RA). A fast, reproducible and sensitive method of liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the quantification of baricitinib in rat plasma has been developed. Irbersartan was used as the internal standard (IS). Baracitinib and IS were extracted from plasma by liquid-liquid extraction using a mixture of n-hexane and dichloromethane (1:1) as extracting agent. Chromatographic separation was performed using Acquity UPLC HILIC BEH 1.7 µm 2.1 × 50 mm column with the mobile phase consisting of 0.1% formic acid in acetonitrile and 20 mM ammonium acetate (pH 3) (97:3). The electrospray ionization in the positive-mode was used for sample ionization in the multiple reaction monitoring mode. Baricitinib and the IS were quantified using precursor-to-production transitions of m/z 372.15 > 251.24 and 429.69 > 207.35 for baricitinib and IS, respectively. The method was validated according to the recent FDA and EMA guidelines for bioanalytical method validation. The lower limit of quantification was 0.2 ng/mL, whereas the intra-day and inter-day accuracies of quality control (QCs) samples were ranged between 85.31% to 89.97% and 87.50% to 88.33%, respectively. Linearity, recovery, precision, and stability parameters were found to be within the acceptable range. The method was applied successfully applied in pilot pharmacokinetic studies.

Validated Reversed-Phase Liquid Chromatographic Method with Gradient Elution for Simultaneous Determination of the Antiviral Agents: Sofosbuvir, Ledipasvir, Daclatasvir, and Simeprevir in Their Dosage Forms.

A simple, rapid, sensitive, and precise reversed-phase liquid chromatographic method was developed and validated for the simultaneous determination of four direct-acting antivirals, sofosbuvir (SF), ledipasvir (LD), declatasvir (DC), and simeprevir (SM), in their respective pharmaceutical formulations. Effective chromatographic separation was achieved on an Agilent Eclipse plus C8 column (250 mm × 4.6 mm, 5 µm) at 40 °C with gradient elution using a mobile phase composed of acetonitrile:phosphate buffer (pH 6.5). The quantification of SF and DC was based on peak area measurements at 260 nm, while the quantification of LD and SM was achieved at 330 nm. The linearity was acceptable from 1.0 to 20.0 µg/mL for the studied drugs, with correlation coefficients >0.999. The analytical performance of the newly proposed HPLC procedure was thoroughly validated according to ICH guidelines in terms of linearity, precision (RSD%, 0.39-1.57), accuracy (98.05-101.90%), specificity, limit of detection (LOD) (0.022-0.039 µg/mL), limit of quantification (LOQ) (0.067-0.118 µg/mL), and robustness. The validated HPLC method was successfully used to analyze the abovementioned drugs in their pure and dosage forms without interference from common excipients present in commercial formulations.

Pharmacy students attitude and perception toward working in community pharmacy in Saudi Arabia.

OBJECTIVE: The objective of this study is to determine the level of attitude and perception of Saudi pharmacy students toward working in community pharmacies after graduation and to assess cultural, educational, and job related barriers and limitations that interfere with students and community pharmacy as a favorable workplace. METHODS: A cross sectional questionnaire, was mailed to a random sample of 600 pharmacy students. It included questions on students' future careers, ideal environment and barriers that might face them in community pharmacy. RESULTS: Four hundreds and twelve (412) completed the survey (response rate was 69%). Mean age was 23 years and 51.2% of respondents were female. Our results revealed low responses toward how interested they are to work in community pharmacy. The study response showed that improvement in salary and money incomes (46%) and culture and society issue (45%) are the two main barrier to make the career in community pharmacy more attractive. CONCLUSIONS: Saudi pharmacy students had a negative attitudes and insufficient knowledge about community pharmacy. Pharmacy school would have an important role to fill the knowledge gap and prepare the student to work in the community pharmacy. In order to successfully "Saudization" the community pharmacy setting, efforts should be made to overcome their perceived barriers.

UPLC-MS/MS assay for quantification of an inhibitor of kinases (Foretinib) in plasma: Application to a pharmacokinetic study in rats.

Foretinib, an oral multikinase inhibitor, is known to have anti-tumor effects against cancers. The doses and the levels of foretinib vary based on the type of cancer to be treated. An accurate and precise method is required to determine the level of foretinib and its pharmacokinetics. Here, we developed such a method, which was validated based on the guidelines of the FDA and EMA. Foretinib and ibrutinib (the internal standard (IS)) were extracted using tert-butyl methyl ether. Foretinib and IS were eluted in approximately 1.2 min. Thus, a linear, fast, accurate, and precise method was developed. The calibration curve was linear (r2 ˃ 0.997) in the range of 0.5-400.0 ng/mL and the lowest limit of quantitation was 0.5 ng/mL. The average recovery, accuracy, and precision were 87.9%, 88.7%, and ≤7.8%, respectively. The analyte was deemed stable using various stability tests. The validated assay was then fruitfully applied to a pharmacokinetics study in rats, which revealed that foretinib was absorbed and the maximum concentration achieved at 4.0 h after the administration of a single dose of foretinib.

Genotoxic impact of long-term cigarette and waterpipe smoking on DNA damage and oxidative stress in healthy subjects.

Although a plethora of studies have examined tobacco smoke-cancer disease association, the involvement of cellular genetic toxicity remains unclear. Therefore, the present study provides molecular evidence for a pathway involved in the DNA damage induced by long-term cigarette and waterpipe smoke in human subjects. The study population consisted of 45 subjects who were divided into three groups; healthy nonsmokers group, cigarette smokers group, and waterpipe smokers group. A questionnaire and consent form was distributed and signed by all participants. Total RNA was extracted from the blood using PAXgene Blood RNA Kit and mRNA expression levels of target genes were quantified by RT-PCR. Our results showed that 80% of the participants smoke 20-39 cigarettes/day, whereas 12% smoke more than 40 cigarettes/day. With regard to waterpipe smoke, the majority (46%) smoke more than 5 times/week. Both cigarette and waterpipe smokers showed increased the plasma levels 8-hydroxy-2'-deoxyguanosine (8-OHdG), of DNA damage marker. In addition, the mRNA expression levels of DNA repair genes (OGG1 and XRCC1) were significantly inhibited in both cigarette and waterpipe smokers groups by 30% and 60%, respectively. This was associated with a marked decrease (50%) in the expression of detoxifying genes (NQO1 and GSTA1) with an increase in CYP1A1 mRNA expression, a cancer-activating gene. Both cigarette and waterpipe smokers increased in the plasma concentrations of several toxic heavy metals such as Cd (130%), Pb (47%), and Ni (30%). In conclusion: the present findings clearly explore the genotoxic effect of cigarette and waterpipe smoking on human DNA.

Advancing pharmaceuticals and patient safety in Saudi Arabia: A 2030 vision initiative.

Low-quality medicines deliver sub-optimal clinical outcomes and waste precious health resources. It is important to ensure that public funds are spent on healthcare technologies that meet national regulatory bodies such as the Saudi Food and Drug Authority (SFDA), quality standards for safety, efficacy, and quality. Medicines quality is a complicated combination of pre-market regulatory specifications, appropriate sourcing of ingredients (active pharmaceutical ingredient (API), excipients, etc.), manufacturing processes, healthcare ecosystem communications, and regular and robust pharmacovigilance practices. A recent conference in Riyadh, sponsored by King Saud University, sought to discuss these issues and develop specific policy recommendations for the Saudi 2030 Vision plan. This and other efforts will require more and more creative educational programs for physicians, pharmacists, hospitals, and patients, and, most importantly evolving regulations on quality standards and oversight by Saudi health authorities.

Synthesis and potential antitumor activity of 7-(4-substituted piperazin-1-yl)-4-oxoquinolines based on ciprofloxacin and norfloxacin scaffolds: in silico studies.

The potential antitumor activities of a series of 7-(4-substituted piperazin-1-yl)fluoroquinolone derivatives (1-14a,b) using ciprofloxacin and norfloxacin as scaffolds are described. These compounds exhibit potent and broad spectrum antitumor activities using 60 human cell lines in addition to the inherent antibacterial activity. Compounds 1a, 2a, 3b, 6b and 7a were found to be the most potent, while 2b, 5b, and 6a were found to have an average activity. The results of this study demonstrated that compounds 1a, 2a, 3b, 6b and 7a (mean GI50; 2.63-3.09 µM) are nearly 7-fold more potent compared with the positive control 5-fluorouracil (mean GI50; 22.60 µM). More interestingly, compounds 1a, 2a, 3b, 6b and 7a have an almost antitumor activity similar to gefitinib (mean GI50; 3.24 µM) and are nearly 2-fold more potent compared to erlotinib (mean GI50; 7.29 µM). In silico study and ADME-Tox prediction methodology were used to study the antitumor activity of the most active compounds and to identify the structural features required for antitumor activity.

Evaluation of knowledge of Health care professionals on warfarin interactions with drug and herb medicinal in Central Saudi Arabia.

OBJECTIVES: To evaluate health care professionals' knowledge on warfarin interactions with drugs and herbs. METHODS: A self-administered questionnaire was developed to assess health care professionals' knowledge on warfarin interactions with drug and herb. Respondents were asked to classify 15 drugs that may effect on warfarin action as "enhance", "inhibit ", "no effect". The study sample involved health care professionals (physicians, pharmacists and nurses) from king Salman hospital, Saudi Arabia. RESULTS: About 92.2% of health care professionals identified warfarin interactions with aspirin, 4.4% for warfarin and fluoxetine. Warfarin and cardiac agents (atenolol) was correctly identified by 11.1% of respondents. In warfarin -herb interactions section, the majority of respondents (66.7%) identified the interaction between green tea and warfarin. Approximately one-third of respondents (n=33) correctly classified warfarin interactions with cardamom. No significant difference was found between the health care professionals (p=0.49) for warfarin-drug interactions knowledge score and p= 0.52 for warfarin- herb interactions knowledge score. CONCLUSION: This study suggests that health care professionals' knowledge of warfarin- drug-herb interactions was inadequate. Therefore, health care professionals should receive more education programs about drug-drug/herb interactions to provide appropriate patient counseling and optimal therapeutic outcomes.

Parents' Hesitancy to Vaccinate Their 5-11-Year-Old Children Against COVID-19 in Saudi Arabia: Predictors From the Health Belief Model.

Data exploring parents' hesitancy to vaccinate their 5-11-year-old children against COVID-19, and associated factors, is limited. This study aims to investigate parents' beliefs and intentions to vaccinate their 5-11-year-old children using the Health Belief Model in Saudi Arabia. A national, cross-sectional, questionnaire-based study was conducted in November, 2021. The self-administered online questionnaire was distributed to a random sample of parents. Adult parents with at least one 5-11-year-old child were included. The main outcome was parents' intention to vaccinate their 5-11-year-old children. Variability in parents' intention was assessed by demographics, COVID-19-related factors, children's health status, and constructs from the Health Belief Model. Univariate and multivariable logistic regression were used to investigate each factor and adjust for the intervariable effect on parental intention to vaccinate their children. Of the 4,135 participants, 61.9% were hesitant to vaccinate their 5-11-year-old children. Parents aged 31 to 40 years (OR = 1.23; 95% CI, 1.02-1.49) and females (OR = 1.52; 95% CI, 1.25-1.84) had higher odds of being hesitant to vaccinate their children than parents from other groups. Parents who perceived low benefit from the vaccine (OR = 16.3; 95% CI, 12.1-21.9) or who had safety or efficacy concerns (OR = 3.76; 95% CI, 3.10-4.58) were among the most hesitant to vaccinate their children. In conclusion, vaccine hesitancy is prevalent among parents of 5-11-year-old children in Saudi Arabia and those who had beliefs of minimal benefits or lack of safety from the COVID-19 vaccine were more hesitant. Government efforts must be directed toward increasing parents' vaccine awareness and tackling the constructs of the Health Belief Model through a well-designed vaccination campaign.

Corrigendum: Parents' Hesitancy to Vaccinate Their 5-11-Year-Old Children Against COVID-19 in Saudi Arabia: Predictors From the Health Belief Model.

[This corrects the article DOI: 10.3389/fpubh.2022.842862.].

Career Readiness Among Saudi Pharmacy Students: Exploring the Need for and the Impact of Career Counseling Services.

Purpose: Employers place emphasis on graduates' work experience and interpersonal skills while academia mainly focuses on developing students' learning ability. One proposed strategy is through career guidance by universities; however, supportive evidence is lacking. This study explored the career readiness of pharmacy students for the Saudi job market. It also examined the availability of career guidance services for pharmacy students and alumni in Saudi Arabia and the impact of such services on recipients' career path choices and development of competencies. Subjects and Methods: This cross-sectional study utilized an online-based survey. Pharmacy students in the last three years of their program and recent graduates participated in the survey. The study used descriptive statistics to describe participants' demographic data. Respondents were asked to rate aspects related to career readiness on a 5-point Likert scale, and their responses were reported as frequencies with percentages or means as appropriate. Comparisons between groups were made using t-test or one- way ANOVA as required. Results: A total of 576 responses were collected. About 25% of participants acknowledged the career guidance services provided at their pharmacy college, whereas the majority indicated that they have never reached out to a career counselor at their university (89.6%). The highest level of disagreement was noticed in impact of career guidance services on participants' establishment of their CV/portfolio (50.7%). Using the work readiness scale, the lowest mean was seen in the social intelligence domain (3.64 ± 0.94). Conclusion: Although substantial proportion of students reported the presence of career guidance services in their university or college, very few stated that they had utilized such services. This could have impacted the students' career readiness for the rapidly changing Saudi job market. Therefore, proper measures to advertise the availability of career guidance services in Saudi pharmacy schools have to be implemented.

Prenatal Exposure to Gabapentin Alters the Development of Ventral Midbrain Dopaminergic Neurons.

Background: Gabapentin is widely prescribed as an off-label drug for the treatment of various diseases, including drug and alcohol addiction. Approximately 83-95% of the usage of gabapentin is off-label, accounting for more than 90% of its sales in the market, which indicates an alarming situation of drug abuse. Such misuse of gabapentin has serious negative consequences. The safety of the use of gabapentin in pregnant women has always been a serious issue, as gabapentin can cross placental barriers. The impact of gabapentin on brain development in the fetus is not sufficiently investigated, which poses difficulties in clinical decisions regarding prescriptions. Methods: The consequences effect of prenatal gabapentin exposure on the development of ventral midbrain dopaminergic neurons were investigated using three-dimensional neuronal cell cultures. Time-mated Swiss mice were used to isolate embryos. The ventral third of the midbrain was removed and used to enrich the dopaminergic population in 3D cell cultures that were subsequently exposed to gabapentin. The effects of gabapentin on the viability, ATP release, morphogenesis and genes expression of ventral midbrain dopaminergic neurons were investigated. Results: Gabapentin treatment at the therapeutic level interfered with the neurogenesis and morphogenesis of vmDA neurons in the fetal brain by causing changes in morphology and alterations in the expression of key developmental genes, such as Nurr1, Chl1, En1, Bdnf, Drd2, and Pitx3. The TH + total neurite length and dominant neurite length were significantly altered. We also found that gabapentin could halt the metabolic state of these neuronal cells by blocking the generation of ATP. Conclusion: Our findings clearly indicate that gabapentin hampers the morphogenesis and development of dopaminergic neurons. This implies that the use of gabapentin could lead to serious complications in child-bearing women. Therefore, caution must be exercised in clinical decisions regarding the prescription of gabapentin in pregnant women.