Identification of phase-I and phase-II metabolites and the metabolic pathway of the novel synthetic cannabinoid 5F-EDMB-PICA in vitro.

5F-EDMB-PICA is a newly emerged synthetic cannabinoid which has been characterized in relevant literature in recent years. Although phase-I metabolites of 5F-EDMB-PICA have been partly reported, the phase-II metabolism of this synthetic cannabinoid has not been studied yet. In this study, we established a phase-I and phase-II metabolism model in vitro by using pooled human liver microsomes, NADPH regeneration system, and UGT incubation system, with 1 mg/ml 5F-EDMB-PICA added and incubated at 37 °C for 60 min. The metabolites were analyzed by Q Exactive™ Hybrid Quadrupole-Orbitrap™ Mass Spectrometer, via which we discovered and identified 14 phase-I metabolites and 4 phase-II metabolites of 5F-EDMB-PICA, involving pathways such as ester hydrolysis, dehydrogenation, hydrolytic defluorination, hydroxylation, dihydroxylation, glucuronidation, and combinations of the pathways mentioned above. We recommend considering the monohydroxylation metabolites (M9, M10) with higher content and intact ester and 5-fluoropentyl structures as potential biomarkers of 5F-EDMB-PICA.

Pagophagia: A case series.

Pica, in the form of ingestion of various non-food items like clay, chalks, etc., is commonly reported in Indian settings, but its other variant, pagophagia (ice eating), gets attention rarely. This case series is about three female patients who presented in psychiatry outpatient clinics with various mental health issues and ice eating habits. A diagnosis of iron deficiency anemia was common among all three cases, and they were managed with oral iron supplementation along with appropriate psychiatric treatments. Pagophagia is an important clinical presentation to be looked for in the changing Indian society.

Isolated cerebellar stroke in a paediatric patient with typical haemolytic uraemic syndrome: a case report and literature review.

Haemolytic Uraemic Syndrome (HUS) is a rare medical condition characterised by microangiopathic haemolytic anaemia, thrombocytopenia, and acute kidney injury. Neurological complications are documented but rarely involve the cerebellum. We present a unique case of a 23-month-old male with HUS triggered by Escherichia coli-O157 (E.coli-O157) infection leading to an isolated cerebellar stroke.The patient initially presented with fever, bloody stools, and seizures. Confirmation of E.coli-O157 infection was obtained, and MRI revealed an isolated cerebellar stroke. Treatment included supportive care, anticoagulation for a right atrial thrombus, with gradual improvement observed.This case highlights the unusual occurrence of isolated cerebellar stroke in HUS patients, emphasising the importance of promptly recognizing manifestations of the central nervous system and the necessity for a multidisciplinary approach. Finally, a comprehensive literature review was conducted to identify cases of HUS patients with cerebellar involvement.

Vertebral Artery Dissection in a Young Adult: A Case Report.

Vertebral artery dissections (VAD) pose a significant risk for strokes, particularly in young adults. This case report details the presentation and management of a 48-year-old patient who was diagnosed with an extracranial VAD following cervical spine manipulation (CSM). The patient's symptoms included acute right-sided ataxia, giddiness, vertigo, nausea, vomiting, and persistent pain behind the right ear, prompting immediate evaluation. After ruling out acute intracerebral hemorrhages, a computed tomography angiogram (CTA) of the head and neck identified a severe narrowing of the right distal vertebral artery with a string sign at the level of the right C1 loop (V3 segment), indicating an extracranial VAD. This finding was further supported when ultrasound (US) imaging revealed a high resistance flow pattern in the right distal vertebral artery. Furthermore, T2 and diffusion-weighted magnetic resonance imaging (MRI) confirmed a 1.8 cm VAD/hematoma and a 1.4 cm acute/subacute infarct in the right posterior inferior cerebellar artery (PICA) territory. This research accentuates the importance of recognizing and addressing that neck pain can be a symptom of musculoskeletal dysfunction or could have neurovascular origins. In this case, the patient's neck pain may have been musculoskeletal or could have been due to a previous dissection. Thus, differentiation should be considered before cervical spine manipulation.

West Nile virus surveillance using sentinel birds: results of eleven years of testing in corvids in a region of northern Italy.

The natural transmission cycle of West Nile virus (WNV) involves birds as primary hosts and mosquitoes as vectors, but this virus can spread to mammals, human beings included. Asymptomatic infected donors pose a risk to the safety of blood transfusions and organ transplants, as WNV can be transmitted through these medical procedures. Since 2009, the region of Emilia-Romagna in northern Italy has been implementing an integrated surveillance system in order to detect WNV circulation in the environment at an early stage. Here we report the results of the two components of the surveillance system, the active testing of corvids and humans, and demonstrate that bird surveillance alone improves a surveillance system based solely on human case detection. As WNV risk reduction measures are applied on a provincial basis, we assessed the ability of this surveillance system component to detect virus circulation prior to the notification of the first human case for each province. Overall, 99 epidemic seasons were evaluated as a result of 11 years (2013-2023) of surveillance in the nine provinces of the region. In this period, 22,314 corvids were tested for WNV and 642 (2.9%) were found to be infected. WNV was generally first detected in birds in July, with sample prevalence peaks occurring between August and September. During the same period, 469 autochthonous human cases were notified, about 60% of which were reported in August. WNV was detected 79 times out of the 99 seasons considered. The virus was notified in birds 73 times (92.4%) and 60 times (75.9%) in humans. WNV was first or only notified in birds in 57 seasons (72.1%), while it was first or only notified in humans in 22 seasons (27.8%). Active surveillance in corvids generally allows the detection of WNV before the onset of human cases. Failure of virus detection occurred mainly in seasons where the number of birds tested was low. Our results show that active testing of a minimum of 3.8 corvids per 100 km2 provides a satisfactory timeliness in the virus detection, but for early detection of WNV it is crucial to test birds between mid-June and mid-August.

Multiple Rare Anatomic Variations in Anterior and Posterior Cerebral Circulation: A Case Report.

Anatomic variations of intracranial arteries are of paramount importance in neurosurgery and interventional radiology. Three extremely rare arterial variants were found by observing the intracranial vascular anatomy on the magnetic resonance angiography files of a 56-year-old female patient. Firstly, on the left side of the vertebrobasilar axis, a persistent primitive lateral basilovertebral anastomosis was found uniting the left anterior inferior and posterior inferior cerebellar arteries; further, the left anterior inferior cerebellar artery looped above the nerves of the internal auditory canal. Secondly, the right posterior inferior cerebellar artery was shown to be leaving the vertebral artery and had a distal fenestration of the telovelotonsillar segment. Such cases of distal fenestrated posterior inferior cerebellar artery are rare. Thirdly, a partly duplicated anterior communicating artery was also found in the anterior circulation. In conclusion, magnetic resonance angiography helps distinguish and detail discrete and delicate rare arterial variants.

Causes and management of Pica disorder among central Iraqi peoples.

OBJECTIVE: Aim: To find the causes and factors behind the Pica disorder, which helps in early diagnosis and appropriate treatments.. PATIENTS AND METHODS: Materials and Methods: A retrospective cross-section study was carried out between July 1, 2022, and April 20, 2023, enrolling 300 patients from different provinces of central and south Iraq with Pica disease whose diagnosis depended on specialized physicians according to WHO guidelines. The participants were following up for three to six months in private clinics. RESULTS: Results: 92.4% of the patients were female, and 41% of patients were under 20 years old, with low ferritin, HB, and vitamin D levels (80% of cases), and these markers showed a negative correlation with the number of Pica. Chowing of ice and clay were the common types of Pica, which represent about 30% each, while 34% of cases had multiple types, which had signs and symptoms of fever, palpitation, vomiting, abdominal pain, paleness, headaches, and hair loss. Six-month flows were better than three months. CONCLUSION: Conclusions: Pica was a disorder that could lead to behavior and emotional abnormalities that caused the patients to eat some things that were eaten by healthy people. This may be, as concluded from our results, due to reduced levels of ferritin, hemoglobin (Hb), and vitamin D that caused these psychological problems.

Pantoea Species Bacteremia in a Child With Sickle Cell Disease: A Case Report.

The Pantoea genus of bacteria is a group of Gram-negative rod-shaped bacteria in the Enterobacteriaceae family. It is an uncommon cause of infection in humans except in specific settings, including hospital-acquired infections and in immunocompromised patients. In this report, we describe the case of a 12-year-old girl with sickle cell disease who presented with a picture of sepsis and was found to have Pantoea species in her blood culture which was treated with antibiotics with a good response. From our literature review, risk factors were identified in the reported cases, for which further exploration is highly recommended.

Serum Level of 25-Hydroxyvitamin D and Symptoms of Pica Among Adolescent School Children in Northern Sudan: A Cross-Sectional Study.

Objectives. To assess levels of 25(OH)D among adolescents with symptoms of pica in northern Sudan. Methods. A cross-sectional study was conducted in North Sudan. Questionaries were used to collect adolescents' sociodemographics. The enzyme-linked immunosorbent assay was used to measure 25(OH)D level. Results. Of the 344 adolescents enrolled, 161 (46.8%) and 183 (53.2%) were male and female, respectively and 103 (29.9%) had symptoms of pica. The median (IQR) of 25(OH)D level was significantly lower in adolescents with symptoms of pica. Multiple linear regression analysis showed that while age (coefficient = 1.1, P = .023) was positively associated with 25(OH)D level, female sex (coefficient = -7.5, P < .001), and pica symptoms (coefficient = -3.5, P = .032) were negatively associated with 25(OH)D level. Conclusion. Adolescents with symptoms of pica had lower 25(OH)D levels. Adolescents with symptoms of pica have to be assessed for vitamin D status.

Posterior Inferior Cerebellar Artery-Posterior Inferior Cerebellar Artery Bypass versus Occipital Artery-Posterior Inferior Cerebellar Artery Bypass for Treating Posterior Circulation Aneurysms: A Systematic Review and Comparative Meta-Analysis.

BACKGROUND: When traditional therapies are unsuitable, revascularization becomes essential for managing posterior inferior cerebellar artery (PICA) or vertebral artery aneurysms. Notably, the PICA-PICA bypass has emerged as a promising option, overshadowing the occipital artery-PICA (OA-PICA) bypass. The objective was to compare the safety and efficacy of OA-PICA and PICA-PICA bypasses. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, we conducted a systematic review and meta-analysis to evaluate the safety and efficacy of OA-PICA and PICA-PICA bypasses for treating posterior circulation aneurysms. RESULTS: We analyzed 13 studies for the PICA-PICA bypass and 16 studies on the OA-PICA bypass, involving 84 and 110 patients, respectively. The median average follow-up for PICA-PICA bypass was 8 months (2-50.3 months), while for OA-PICA, it was 27.8 months (6-84 months). The patency rate for OA-PICA was 97% (95% confidence interval [CI]: 92%-100%) and 100% (95% CI: 95%-100%) for PICA-PICA. Complication rates were 29% (95% CI: 10%-47%) for OA-PICA and 12% (95% CI: 3%-21%) for PICA-PICA. Good clinical outcomes were observed in 71% (95% CI: 52%-90%) of OA-PICA patients and 87% (95% CI: 75%-100%) of PICA-PICA patients. Procedure-related mortality was 1% (95% CI: 0%-6%) for OA-PICA and 1% (95% CI: 0%-10%) for PICA-PICA. CONCLUSIONS: Both procedures have demonstrated promising results in efficacy and safety. PICA-PICA exhibits slightly better patency rates, better clinical outcomes, and fewer complications, but with a lack of substantial follow-up and a smaller sample size. The choice between these procedures should be based on the surgeon's expertise and the patient's anatomy.

GC-MS/MS analysis of synthetic cannabinoids 5F-MDMB-PICA and 5F-CUMYL-PICA in forensic cases.

Aim: Validate a method to quantify 1-(5-fluoropentyl)-N-(2-phenylpropan-2-yl)-1H-indole-3-carboxamide (5F-CUMYL-PICA) and methyl 2-[[1-(5-fluoropentyl) indole-3-carbonyl] amino]-3,3-dimethyl-butanoate (5F-MDMB-PICA) in blood samples using GC-MS/MS. Materials & methods: A solid-phase extraction (SPE) method has been developed to quantify 5F-MDMB-PICA and 5F-CUMYL-PICA in authentic human blood samples. Results & conclusion: The limit of detection (LOD) was 0.1 and 0.11 ng/ml for 5F-CUMYL-PICA and 5F-MDMB-PICA, respectively, while the limit of quantification (LOQ) was 0.50 ng/ml for both two compounds. Recovery was 91.40, 82.54 and 85.10% for SPE, supported liquid extraction (SLE) and ISOLUTE C18; matrix effects 15, 24 and 22.5% for SPE, SLE and ISOLUTE C18; accuracy was 2.4-5.5 and 3.9-7.3% for SPE, SLE and ISOLUTE C18, while precision was 4.6-7.7 and 6.4-8.3% for SPE, SLE and ISOLUTE C18, respectively. The concentrations of 5F-CUMYL-PICA and 5F-MDMB-PICA in the authentic human blood samples were 2.18 and 3.07 ng/ml, respectively. The validated method was successfully used in supporting the quantification of analytes in blood.

[Box: see text].

Opalski Syndrome and Elucidation of Lateral Medullary Syndrome.

In this case, a 61-year-old patient presented with Horner's syndrome of the left eye, left-sided truncal ataxia, left-sided pain/paresthesia of the face as well as right-sided loss of pain and temperature of the arms and legs. MRI findings displayed a clear 4 mm acute left lateral medullary infarct of the left posterior inferior cerebellar artery (PICA) vascular territory, indicative of lateral medullary syndrome (LMS). The presence of pre-existing medical conditions such as uncontrolled diabetes, late-stage syphilis, and a mechanical aortic valve complicated this clinical picture. The presence of ipsilateral corticospinal deficits in this patient revealed Opalski syndrome, a rare variant of LMS. This case report highlighted the importance of correlating imaging and physical examination of stroke findings.

Synthesis, structural characterization, analytical profiling, and application to authentic samples of synthesized Phase I metabolites of the synthetic cannabinoid 5F-MDMB-PICA.

5F-MDMB-PICA, an indole-type synthetic cannabinoid (SC), was classified illicit globally in 2020. Although the extensive metabolism of 5F-MDMB-PICA in the human body warrants the development of robust analytical methods for metabolite detection and quantification, a current lack of reference standards for characteristic metabolites hinders such method creation. This work described the synthesis of 18 reference standards for 5F-MDMB-PICA and its possible Phase I metabolites, including three hydroxylated positional isomers R14 to R16. All the compounds were systematic characterized via nuclear magnetic resonance, Fourier transform infrared spectroscopy, and high-resolution mass spectrometry. Furthermore, two methods were developed for the simultaneous detection of all standards using liquid chromatography-tandem mass spectrometry and ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. By comparison with authentic samples, R17 was identified as a suitable urine biomarker for 5F-MDMB-PICA uptake.

Pica behavior of laboratory rats (Rattus norvegicus domestica): Nauseated animals ingest kaolin, zeolite, bentonite, but not calcium carbonate chalk.

"Pica" refers to the ingestion of non-nutritive substances by animals that would not typically consume them. The pica behavior can be utilized to investigate the internal conditions of animals' bodies. For example, rats, due to neuroanatomical reasons, cannot vomit; nevertheless, when nauseated, they ingest kaolin clay. This renders the ingestion of kaolin a practical proxy for measuring nausea in rats. The question of whether rats consume minerals other than kaolin during nauseous episodes remains unanswered. This study aims to identify a mineral better suited for detecting nausea in rats. In two experiments, nausea was induced in laboratory rats by a single dose of lithium chloride (0.15 M, 2% bw), and their mineral consumption over the 24-hour period was measured. Experiment 1 compared three minerals between rat groups: kaolin sold for nausea detection (kaolin A), kaolin for ceramics (kaolin B), and zeolite. Nauseated rats consumed all minerals, with the highest consumption occurring with kaolin B. In Experiment 2, three commercially available health soils were compared: edible kaolin, edible bentonite, and edible chalk. The most significant consumption was observed in the kaolin group, followed by the bentonite group, while nauseated rats did not consume edible chalk. These findings underscore the suitability of kaolin for nausea detection, although the extent of consumption may vary depending on the product.

Research on feeding and eating disorders in India: A narrative review.

Despite growing evidence of their prevalence, research on feeding and eating disorders (FEDs) in India has been sporadic. This narrative review aimed to summarize the research on FED in India and set priorities for future research and translation of evidence. An electronic search was conducted in the MEDLINE, PsycINFO, and Google Scholar databases to identify relevant English peer-reviewed articles from April 1967 to July 2023. The extracted data from these studies included author names, publication year, research location, type of intervention (for interventional studies), nature of comparator treatments, and main outcomes or findings. We found a rising trend in the prevalence of EDs in India. Adolescent age group, female sex, higher socioeconomic status, family history of mental illness or disordered eating, and borderline personality pattern were risk factors for EDs. For feeding disorders (FDs), childhood age group, malnutrition, pregnancy, psychosis, intellectual disability (ID), and obsessive-compulsive disorder (OCD) were putative risk factors. Both physical and psychiatric comorbidities were common in FEDs. Culture appears to exert a pathoplastic effect on symptom presentation in FEDs; an illustrative example is the documented nonfat phobic variant of anorexia nervosa (AN) in India. Research on management has focused on using assessment tools, investigations to rule out medical comorbidities, psychosocial and family-based psychotherapies, nutritional rehabilitation, pharmacotherapy, and neuromodulation approaches. Whereas the publication output on FEDs in India has increased over the last decade, it remains an under-researched area, with a striking paucity of original research. Future research priorities in FEDs include conducting country-wide registry-based studies to offer real-world insights, longitudinal research to identify culturally relevant risk factors, and developing brief, culturally sensitive diagnostic instruments for FEDs in the Indian context. This will help generate locally relevant epidemiological data on FEDs and inform treatment and prevention strategies.

Posterior Inferior Cerebellar Artery Aneurysm Shaped Like a "Calabash Gourd" and Mimicking a Tumor.

Posterior inferior cerebellar artery aneurysms are likely to be fusiform, yet they hardly enlarge to mimic a tumor in the posterior fossa on radiology. They constitute about 3%-4% of all cerebral aneurysms. A 65-year-old woman presented with tremor in her right upper limb for 1 year and intermittent dizziness for 8 months. Interestingly, magnetic resonance imaging revealed 2 unanimously enhanced masses like mother and daughter located in the right cerebellum hemisphere. The lesion was resected via surgery, and histopathology established the diagnosis of an aneurysm. Her tremor and dizziness subsided 3 months after the surgery, and at her 2-year follow-up she was well with no further neurologic deficits.

Relationship of self-reported pica and avoidant restrictive food intake disorder symptomology with dimensions of impulsivity, perceived stress among Pakistani University students.

INTRODUCTION: Pica and avoidant/restrictive food intake disorder are two of the three new eating and feeding disorders introduced in the DSM-5, this inclusion has drawn attention to the immediate need for research into their prevalence, diagnostic assessment, underlying risk factors and optimal treatment. There are very few studies available that explored the predictors or causes of these eating disorders specifically in Pakistani context. OBJECTIVES: The objectives of the current study include (a) to estimate the presence of pica and avoidant/restrictive food intake disorder symptomology among young adults in Pakistan, (b) to examine the relationship between dimensions of impulsivity, stress and presence of pica and avoidant/restrictive food intake disorder, (c) to explore the mediation role of stress. METHODS: The sample consisted of 660 young adults with age range 18-25 years, recruited through convenient sampling. The respondents were provided with a questionnaire comprising of an informed consent, a demographic information sheet and self-report measures including PARDI-AR-Q to assess symptomology of pica and avoidant/restrictive food intake disorder, UPPS-P Impulsive Behaviour Scale to assess dimensions of impulsivity and Perceived Stress Scale to measure perceived stress. RESULTS: The findings show that 28 participants (4.2%) reported Pica symptomology, of which eleven participants indicated that they currently consume more than one non-food item. 19 respondents (2.8%) reported avoidant/restrictive food intake disorder symptomology. 13 respondents reported varying degrees of all three symptom clusters namely sensory based food avoidance, lack of interest in food, and fear of negative consequences of eating. Additionally, each of the dimensions of impulsivity was found to be positively correlated to the presence of pica and avoidant/restrictive food intake disorder. Perceived stress was identified as a mediating factor between each of the dimensions of impulsivity and presence of pica and avoidant/restrictive food intake disorder. CONCLUSION: Although current study focused on a particular age range, it has drawn attention to the necessity of screening and investigating other strata of Pakistani population for pica and avoidant/restrictive food intake disorder. The clinical utility of the present research resided in the identification of factors associated with pica and avoidant/restrictive food intake disorder, an information which can be used to tailor psychological interventions, modify existing ones, and inform the future research on evidence-based treatment.

The study explored pica and avoidant/restrictive food intake disorder in young adults in Pakistan. It found a presence of these disorders and identified connections with impulsivity and stress. These disorders, characterized by unusual eating behaviors and food avoidance, showed links with impulsivity dimensions and stress levels. Importantly, stress seemed to play a role between impulsivity and these disorders. This study emphasizes the need for broader research across different age groups in Pakistan to understand these disorders better. The study suggests that these eating disorders aren't confined to specific demographics, supporting the DSM-5 decision to lift age limits. In essence, this research opens doors for understanding and addressing pica and avoidant/restrictive food intake disorder in diverse populations, fostering a more comprehensive approach to mental health in the context of eating behaviors.

How I do it: endoscopic microvascular decompression for hemifacial spasm associated with anterior inferior cerebellar artery-posterior inferior cerebellar artery common trunk.

BACKGROUND: Multiple vessels from the anterior inferior cerebellar artery-posterior inferior cerebellar artery common trunk (APC) variation of the posterior circulation can cause hemifacial spasm (HFS). METHOD: Endoscopic microvascular decompression (eMVD) was performed using 0° and 30° endoscopes through a retrosigmoid keyhole. The root exit zone (REZ) was decompressed by transpositioning the offending anterior inferior cerebellar artery (AICA) and posterior inferior cerebellar artery (PICA) arising from the APC under excellent endoscopic view. CONCLUSION: eMVD is an advanced, minimally invasive and reliable technique to resolve the neurovascular conflict (NVC) in HFS due to offenders from APC.

Successful Retrieval of 35 Razors From the Stomach via Upper Gastrointestinal (GI) Endoscopy: A Case Report.

Adult ingestion of foreign bodies in the digestive system is a common clinical challenge, often involving mentally impaired individuals, criminals, and drug dealers or occurring accidentally. Encounters with multiple sharp foreign bodies are infrequent and pose significant risks, including gastrointestinal (GI) bleeding, perforation, internal fistulas, and infection. The choice between endoscopy and emergency surgery for removal is contentious, with the less invasive endoscopy typically favored as the first line of management, depending on the foreign body's location and endoscopic accessibility. The current literature on the treatment of numerous sharp foreign bodies is sparse. This case report illustrates the successful endoscopic removal of a large quantity of sharp foreign bodies (35 half blades) from the upper GI tract, utilizing various extraction tools. It also aims to contribute to the existing literature regarding management strategies for ingested sharp foreign bodies. A comprehensive account is provided of the clinical presentation, imaging studies, consultations, and endoscopic procedures performed, culminating in the patient's safe discharge from our facility.

Prevalence and recurrence of pica behaviors in early childhood within the ALSPAC birth cohort.

OBJECTIVE: The present study examined prevalence and correlates of pica behaviors during childhood using data from the Avon Longitudinal Study of Parents and Children (ALSPAC) study. METHOD: Data on 10,109 caregivers from the ALSPAC study who reported pica behavior at 36, 54, 65, 77, and 115 months on their child were included. Autism was obtained through clinical and education records, while DD was derived from the Denver Developmental Screening Test. RESULTS: A total of 312 parents (3.08%) reported pica behaviors in their child. Of these, 19.55% reported pica at least at two waves (n = 61). Pica was most common at 36 months (N = 226; 2.29%) and decreased as children aged. A significant association was found between pica and autism at all five waves (p < .001). There was a significant relationship between pica and DD, with individuals with DD more likely to experience pica than those without DD at 36 (p = .01), and 54 (p < .001), 65 (p = .04), 77 (p < .001), and 115 months (p = .006). Exploratory analyses examined pica behaviors with broader eating difficulties and child body mass index. DISCUSSION: This study enhances understanding of childhood pica behaviors, addressing a significant gap in knowledge. Pica occurrence in the general population is poorly understood due to few epidemiological studies. Findings from the present study indicate pica is an uncommon behavior in childhood; however, children with DD or autism may benefit from pica screening and diagnosis between ages 36 and 115 months. Children who exhibit undereating, overeating, and food fussiness may also engage in pica behaviors.