Update on pathogenesis, management, and control of Plasmodium vivax.

PURPOSE OF REVIEW: This is a review of Plasmodium vivax epidemiology, pathogenesis, disease presentation, treatment and innovations in control and elimination. Here, we examine the recent literature and summarize new advances and ongoing challenges in the management of P. vivax . RECENT FINDINGS: P. vivax has a complex life cycle in the human host which impacts disease severity and treatment regimens. There is increasing data for the presence of cryptic reservoirs in the spleen and bone marrow which may contribute to chronic vivax infections and possibly disease severity. Methods to map the geospatial epidemiology of P. vivax chloroquine resistance are advancing, and they will inform local treatment guidelines. P. vivax treatment requires an 8-aminoquinoline to eradicate the dormant liver stage. Evidence suggests that higher doses of 8-aminoquinolines may be needed for radical cure of tropical frequent-relapsing strains. SUMMARY: P. vivax is a significant global health problem. There have been recent developments in understanding the complexity of P. vivax biology and optimization of antimalarial therapy. Studies toward the development of best practices for P. vivax control and elimination programs are ongoing.

Diagnosis, Treatment, and Prevention of Malaria in the US: A Review.

Importance: Malaria is caused by protozoa parasites of the genus Plasmodium and is diagnosed in approximately 2000 people in the US each year who have returned from visiting regions with endemic malaria. The mortality rate from malaria is approximately 0.3% in the US and 0.26% worldwide. Observations: In the US, most malaria is diagnosed in people who traveled to an endemic region. More than 80% of people diagnosed with malaria in the US acquired the infection in Africa. Of the approximately 2000 people diagnosed with malaria in the US in 2017, an estimated 82.4% were adults and about 78.6% were Black or African American. Among US residents diagnosed with malaria, 71.7% had not taken malaria chemoprophylaxis during travel. In 2017 in the US, P falciparum was the species diagnosed in approximately 79% of patients, whereas P vivax was diagnosed in an estimated 11.2% of patients. In 2017 in the US, severe malaria, defined as vital organ involvement including shock, pulmonary edema, significant bleeding, seizures, impaired consciousness, and laboratory abnormalities such as kidney impairment, acidosis, anemia, or high parasitemia, occurred in approximately 14% of patients, and an estimated 0.3% of those receiving a diagnosis of malaria in the US died. P falciparum has developed resistance to chloroquine in most regions of the world, including Africa. First-line therapy for P falciparum malaria in the US is combination therapy that includes artemisinin. If P falciparum was acquired in a known chloroquine-sensitive region such as Haiti, chloroquine remains an alternative option. When artemisinin-based combination therapies are not available, atovaquone-proguanil or quinine plus clindamycin is used for chloroquine-resistant malaria. P vivax, P ovale, P malariae, and P knowlesi are typically chloroquine sensitive, and treatment with either artemisinin-based combination therapy or chloroquine for regions with chloroquine-susceptible infections for uncomplicated malaria is recommended. For severe malaria, intravenous artesunate is first-line therapy. Treatment of mild malaria due to a chloroquine-resistant parasite consists of a combination therapy that includes artemisinin or chloroquine for chloroquine-sensitive malaria. P vivax and P ovale require additional therapy with an 8-aminoquinoline to eradicate the liver stage. Several options exist for chemoprophylaxis and selection should be based on patient characteristics and preferences. Conclusions and Relevance: Approximately 2000 cases of malaria are diagnosed each year in the US, most commonly in travelers returning from visiting endemic areas. Prevention and treatment of malaria depend on the species and the drug sensitivity of parasites from the region of acquisition. Intravenous artesunate is first-line therapy for severe malaria.

Neuroinflammation changes with periodontal inflammation status during periodontitis in wild-type mice.

OBJECTIVE: To investigate neuroinflammation under different periodontal status. MATERIALS AND METHODS: Experimental periodontitis was induced by molar ligation (Lig group) or periodontal injection of lipopolysaccharide (LPS, Lps group). Periodontal status was assessed by alveolar bone resorption and periodontal inflammation. Micro-computed tomography and haematoxylin-eosin staining were performed to assess alveolar bone resorption and periodontal inflammation, respectively. Neuroinflammation was assessed by glial cell proliferation and proinflammatory factor expression. Microgliosis was determined by immunofluorescence. Astrogliosis was determined by immunohistochemistry. Expressions of tumour necrosis factor-alpha (TNF-α) and interleukin (IL)-1ß were assessed by enzyme-linked immunosorbent assay. RESULTS: Microgliosis and astrogliosis in the Lig group were notable with molar ligation for 2 weeks and 4 weeks (p < .05), but were only slightly different similar from the control group by week 12. Microgliosis and astrogliosis in the Lps group were significant with LPS injection for 4 and 8 weeks (p < .05). The groups displayed a positive correlation between the degree of periodontal inflammation and the number of glial cells (p < .05). Expressions of IL-1ß and TNF-α in the Lps group were significantly increased with LPS injection for 8 weeks (p < .05). In the Lig group, only TNF-α was highly expressed with molar ligation for 12 weeks (p < .05). CONCLUSION: Both models demonstrated that the inflammatory response in the hippocampus of mice can change during periodontitis depending on the periodontal inflammation status.

Correlation between Academic Performance and Anxiety in Medical Students of Majmaah University - KSA.

OBJECTIVE: To study the prevalence of anxiety and its correlation with the academic performance among medical students.. METHODS: The analytical cross-sectional study was conducted over six months from March 2018 to August 2018, at the male and female campuses of the College of Medicine, Majmaah University, Majmaah, Saudi Arabia, and comprised medical students of either gender. Data on anxiety was collected using a selfreporting questionnaire that included the Beck Anxiety Inventory. Academic performance was taken as a measurable record from the cumulative grade point average. Data was analysed using SPSS 24. RESULTS: Of the 247 subjects, 170(68.8%) were males. Anxiety was found in 97(39.3%) of the students. The level of anxiety was significantly higher among females compared to males (p=0.001), among those in the final year (p=0.002), and in those with low academic grades (p=0.016). CONCLUSIONS: Anxiety was found to be common among medical students and it was associated with female gender, low grades and advanced year of studies.

Oxidative and carbonyl stress in pregnant women with obstructive sleep apnea.

PURPOSE: Pregnant women are particularly susceptible to sleep-disordered breathing. Obstructive sleep apnea (OSA) in pregnancy is associated with poor pregnancy and fetal outcomes. Oxidative stress caused by intermittent hypoxemia and reoxygenation may impact pregnancy health. We hypothesize that pregnant women with OSA have a pronounced oxidative stress profile. METHODS: A case-control study was performed to study oxidative stress markers in the serum of pregnant women with or without OSA. Patients with OSA were identified between 2003 and 2009. Contemporaneous controls were pregnant subjects without apnea, gasping, or snoring around the time of delivery. Serum markers of oxidative and carbonyl stress were measured by spectrophotometric/fluorometric methods. Multiple linear regression analysis was used with a model including age, body mass index at delivery, history of diabetes, and gestational age. RESULTS: Serum samples from 23 OSA cases and 41 controls were identified. Advanced oxidation protein products, a marker for oxidative stress, and advanced glycation end products (AGEs), a marker for carbonyl stress, were significantly lower in women with OSA than in controls (p value <0.0001). Total antioxidant capacity was higher in women with OSA in comparison to controls (p value <0.0001). The difference in AGEs remained significant even after adjusting for confounders. CONCLUSION: Contrary to our hypothesis, the results of this study suggest that pregnant women with OSA have higher antioxidant capacity and lower oxidative and carbonyl stress markers compared to controls, suggesting a possible protective effect of intermittent hypoxia. Whether OSA in pregnancy impacts oxidative stress differently than OSA in the general population remains to be confirmed.

Synthesis and in vitro Bio-activity Evaluation of N4-benzyl Substituted 5-Chloroisatin-3-thiosemicarbazones as Urease and Glycation Inhibitors.

A series of fifteen N4-benzyl substituted 5-chloroisatin-3-thiosemicarbazones 5a-o were synthesized and screened mainly for their antiurease and antiglycation effects. Lemna aequinocitalis growth and Artemia salina assays were carried out to determine their phytotoxicity and cytotoxicity potential. All the compounds proved to be extremely effective urease inhibitors, demonstrating enzyme inhibition much better than the reference inhibitor, thiourea (IC50 values 1.31 ± 0.06 to 3.24 ± 0.15 vs. 22.3 ± 1.12 µM). On the other hand, eight out of fifteen compounds tested, i.e. 5b, 5c, 5h-k, 5m and 5n were found to be potent glycation inhibitors. Of these, five viz. 5c, 5h-j and 5n proved to be exceedingly efficient, displaying glycation inhibition greater than the reference inhibitor, rutin (IC50 values 114.51 ± 1.08 to 229.94 ± 3.40 vs. 294.5 ± 1.5 µM).

Synthesis, X-ray molecular structure, biological evaluation and molecular docking studies of some N4-benzyl substituted 5-nitroisatin-3-thiosemicarbazones.

A series of fifteen N4-benzyl substituted 5-nitroisatin-3-thiosemicarbazones 5a-o was synthesized and evaluated for urease inhibitory, phytotoxic and cytotoxic influences. All the compounds proved to be highly potent inhibitors of the enzyme, showing inhibitory activity (IC50=0.87±0.25-8.09±0.23µM) much better than the reference inhibitor, thiourea (IC50=22.3±1.12µM) and may thus act as persuasive leads for further studies. In phytotoxicity assay, twelve out of fifteen thiosemicarbazones tested i.e. 5a-e, 5g, 5i and 5k-o appeared to be active, exhibiting weak or non-significant (5-35%) growth inhibition at the highest tested concentrations (1000 or 500µg/mL). In contrast, only one compound i.e. 5i was active in the brine shrimp (Artemia salina) lethality bioassay, demonstrating cytotoxic activity with LD50 value 2.55×10-5M. Molecular docking studies of compounds 5a-o were also performed to identify their probable binding modes in the active site of the enzyme.

Chloride Depletion Alkalosis as a Predictor of Inhospital Mortality in Patients with Decompensated Heart Failure.

OBJECTIVES: Chloride depletion alkalosis (CDA) is often seen as a consequence of diuresis in heart failure (HF) but its prognostic significance remains unknown. The purpose of this study was to evaluate the prognostic role of CDA in decompensated HF (DHF). METHODS: A retrospective cohort analysis was performed on 674 patients who were admitted with DHF. Patients were assigned to 2 groups based on the change in serum bicarbonate (median = 3 mmol/l) after diuresis, which was calculated by computing the difference in the admission and discharge serum bicarbonate: the CDA group (a change in serum bicarbonate ≥3 mmol/l) and the non-CDA group (change in serum bicarbonate <3 mmol/l). The primary end points were inhospital mortality and the composite end point of all-cause 30-day mortality and hospital readmission for HF. RESULTS: In a multivariable logistic regression model, the CDA group, i.e. 374 patients, had a lower inhospital mortality than the non-CDA group, i.e. 300 patients (OR 0.11, 95% CI 0.03-0.38; p = 0.0005) after adjusting for other covariates. There was no statistically significant difference in the combined end point of all-cause 30-day mortality and readmission between the 2 groups (OR 1.26, 95% CI 0.74-2.12; p = 0.39). CONCLUSION: The presence of CDA during hospitalization for DHF was independently associated with a better inhospital survival rate.

Development and evaluation of a novel in situ gel of sparfloxacin for sustained ocular drug delivery: in vitro and ex vivo characterization.

Conventional eye drops are the most popular delivery systems in the treatment of various eye infections. However, the major problem encountered in these dosage forms is precorneal elimination of the drug, resulting in poor bioavailability and therapeutic response. To overcome the side effects of pulsed dosing, an attempt has been made to formulate and evaluate a novel in situ gelling system of Sparfloxacin for sustained ocular drug delivery (ion and pH triggered gelling system). These gelling systems involve the use of sodium alginate (ion sensitive polymer) used as gelling agent and methylcellulose as viscosity-enhancing agent. The developed formulations were evaluated for clarity, pH, gelling capacity, rheological study, in vitro release study, ex vivo corneal permeation study, ocular irritation studies (HET-CAM test) and histopathological study using isolated goat corneas. The formulations were found to be stable, non-irritant and showed sustained release of the drug for a period up to 24 h with no ocular damage. In situ gel of sparfloxacin could be prepared successfully promising their use in ophthalmic delivery.

Unilateral avascular necrosis of the right hip in an HIV patient with tearing of the rectus femoris and adductor longus muscles.

A man in his 20s with a medical history of syphilis, chlamydia and HIV presented to the emergency department (ED) with 2 months of right hip pain and was found to have advanced avascular necrosis (AVN) of the right femoral head with secondary haemorrhage. The patient lacked the common risk factors of AVN in patients with HIV (PWH): ≥10 years of HIV diagnosis, extended duration on highly active antiretroviral therapy, trauma, corticosteroid use, alcohol abuse, systemic lupus erythematosus, obesity, smoking and dyslipidaemia. Given the extensive destructive changes in the hip joint and muscles, a right hip resection arthroplasty was performed, and the patient recovered well postoperatively. This case presents a learning opportunity for understanding bone pathologies in PWH and offers clinical guidance for the management of HIV-infected patients with a focus on optimising bone health.

Exploring the Versatility of Aerogels: Broad Applications in Biomedical Engineering, Astronautics, Energy Storage, Biosensing, and Current Progress.

Aerogels are unique and extremely porous substances with fascinating characteristics such as ultra-low density, extraordinary surface area, and excellent thermal insulation capabilities. Due to their exceptional features, aerogels have attracted significant interest from various fields, including energy, environment, aerospace, and biomedical engineering. This review paper presents an overview of the trailblazing research on aerogels, aiming at their preparation, characterization, and applications. Various methods of aerogel synthesis, such as sol-gel, supercritical drying, are discussed. Additionally, recent progress in the characterization of aerogel structures, including their morphology, porosity, and thermal properties, are extensively reviewed. Finally, aerogel's utilizations in numerous disciplines, for instance, energy storage, thermal insulation, catalysis, environmental remedy, and biomedical applications, are summarized. This review paper provides a comprehensive understanding of aerogels and their prospective uses in diverse fields, highlighting their unique properties for future research and development.

Understanding role of pesticides in development of Parkinson's disease: Insights from Drosophila and rodent models.

Parkinson's disease is a neurodegenerative illness linked to ageing, marked by the gradual decline of dopaminergic neurons in the midbrain. The exact aetiology of Parkinson's disease (PD) remains uncertain, with genetic predisposition and environmental variables playing significant roles in the disease's frequency. Epidemiological data indicates a possible connection between pesticide exposure and brain degeneration. Specific pesticides have been associated with important characteristics of Parkinson's disease, such as mitochondrial dysfunction, oxidative stress, and α-synuclein aggregation, which are crucial for the advancement of the disease. Recently, many animal models have been developed for Parkinson's disease study. Although these models do not perfectly replicate the disease's pathology, they provide valuable insights that improve our understanding of the condition and the limitations of current treatment methods. Drosophila, in particular, has been useful in studying Parkinson's disease induced by toxins or genetic factors. The review thoroughly analyses many animal models utilised in Parkinson's research, with an emphasis on issues including pesticides, genetic and epigenetic changes, proteasome failure, oxidative damage, α-synuclein inoculation, and mitochondrial dysfunction. The text highlights the important impact of pesticides on the onset of Parkinson's disease (PD) and stresses the need for more research on genetic and mechanistic alterations linked to the condition.

Sensitivity Profile of Fosfomycin, Nitrofurantoin, and Co-trimoxazole Against Uropathogens Isolated From UTI Cases in a Secondary Care Center, KSA.

Background Fosfomycin, nitrofurantoin, and co-trimoxazole are cheap and effective first-line oral antimicrobials in cases of uncomplicated cystitis in males and non-pregnant females. Fosfomycin and nitrofurantoin are called urinary antiseptics because these two drugs are primarily excreted in the kidney and concentrated in the urine without systemic effect. The present study was designed to evaluate the in vitro activities of fosfomycin, nitrofurantoin, and co-trimoxazole against uropathogens isolated at King Khalid Hospital Al-Majmaah, KSA. Methods The study was conducted at the King Khalid Hospital Al Majmaah, KSA, from September 1, 2021, until February 28, 2022. The patients' urine samples were inoculated on the Cystein Lactose Electrolytes Deficient (CLED) medium, and uropathogens were isolated. The organisms' identification and sensitivity testing against cotrimoxazole, fosfomycin, and nitrofurantoin was conducted using a Microscan automated analyzer, the MicroScan WalkAway Beckman Coulter, Sacramento, CA, USA. Results The study comprised non-repeat 137 patients who were either admitted to the hospital or treated as outpatients, yielding a total of 147 isolates. Nitrofurantoin showed a lower resistance rate, around 20% (n = 29), followed by fosfomycin at 23% (n = 34). The resistance rate of cotrimoxazole was 43% (n = 63). Overall, nitrofurantoin and fosfomycin showed relatively lower resistance against all isolates. Conclusions Being cheap and effective, we propose that fosfomycin and nitrofurantoin be used as first-line treatments in patients presenting with uncomplicated UTIs.

Mesenchymal stem cells and their potential therapeutic benefits and challenges in the treatment and pathogenesis of gastric cancer.

Mesenchymal stem/stromal cells (MSCs) are acknowledged for their remarkable ability to undergo differentiation into various cell types. In addition, they exhibit anti-tumor characteristics, prompting endeavors to modify MSCs for employment in cancer therapies. On the contrary, it is imperative to recognize that MSCs have been extensively linked to pathways that facilitate the advancement of tumors. Numerous research studies have sought to modify MSCs for clinical application; however, the outcomes have been ambiguous, potentially due to the heterogeneity of MSC populations. Furthermore, the conflicting roles of MSCs in suppressing and promoting tumor growth present a challenge to the appropriateness of their use in anti-cancer therapies. Currently, there exists a lack of comprehensive comprehension concerning the anti-tumor and pro-tumor characteristics of MSCs for gastric cancer (GC). This article discusses the influence of MSCs on GC, the underlying mechanisms, the origins of MSCs, and their effects. This review article also elucidates how MSCs exhibit dual characteristics of promoting and inhibiting tumor growth. Hence, it is of utmost importance that clinical inquiries aimed at utilizing MSCs as a therapeutic intervention for cancer consider the potentiality of MSCs to accelerate the progression of GC. It is crucial to exercise caution throughout the process of developing MSC-based cellular therapies to enhance their anti-cancer attributes while simultaneously eliminating their tumor-promoting impacts.

Preparation of novel S-allyl cysteine chitosan based nanoparticles for use in ischemic brain treatment.

Objective: To enhance the brain bioavailability of S-allyl-l-cysteine (SC) by developing novel S-allyl-l-cysteine chitosan nanoparticles (SC CS NPs) and examining the quantity of SC by developing a novel method of ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) in ischemic rat brain treatment. Methods: The ionotropic gelation method was used to develop S-allyl cysteine-loaded CS NPs. The 4-factor, 5-level central composite design was optimized to determine the effect of independent variables, i.e., particle size, polydispersity index (PDI), zeta potential, EE, and loading capacity, together with their characterization, followed by drug release and intranasal permeation to enhance the brain bioavailability and examination of their neurobehavioral and biochemical parameters with their histopathological examination. Results: SC CS NPs were optimized at the particle size of 93.21 ± 3.31 nm (PDI: 0.317 ± 0.003), zeta potential of 44.4 ± 2.93, and drug loading of 41.23 ± 1.97% with an entrapment efficiency of 82.61 ± 4.93% having sustain and controlled release (79.92 ± 3.86%) with great permeation (>80.0%) of SC. SC showed the retention time of 1.021 min and 162.50/73.05 m/z. SC showed good linearity in the range of 5.0-1300.0 ng mL-1, % inter-and-intraday accuracy of 96.00-99.06% and CV of 4.38-4.38%. We observed significant results, i.e., p < 0.001 for improved (AUC)0-24 and Cmax delivered via i.v. and i.n. dose. We also observed the highly significantly observations of SC CS NPs (i.n.) based on their treatment results for the biochemical, neurobehavioral, and histopathological examination in the developed ischemic MCAO brain rat model. Conclusion: The excellent significant role of mucoadhesive CS NPs of SC was proven based on the enhancement in the brain bioavailability of SC via i.n. delivery in rats and easy targeting of the brain for ischemic brain treatment followed by an improvement in neuroprotection based on a very small dose of SC.

Ecological momentary assessment and cue-elicited drug craving as primary endpoints: study protocol for a randomized, double-blind, placebo-controlled clinical trial testing the efficacy of a GLP-1 receptor agonist in opioid use disorder.

BACKGROUND: Despite continuing advancements in treatments for opioid use disorder (OUD), continued high rates of relapse indicate the need for more effective approaches, including novel pharmacological interventions. Glucagon-like peptide 1 receptor agonists (GLP-1RA) provide a promising avenue as a non-opioid medication for the treatment of OUD. Whereas GLP-1RAs have shown promise as a treatment for alcohol and nicotine use disorders, to date, no controlled clinical trials have been conducted to determine if a GLP-1RA can reduce craving in individuals with OUD. The purpose of the current protocol was to evaluate the potential for a GLP-1RA, liraglutide, to safely and effectively reduce craving in an OUD population in residential treatment. METHOD: This preliminary study was a randomized, double-blinded, placebo-controlled clinical trial designed to test the safety and efficacy of the GLP-1RA, liraglutide, in 40 participants in residential treatment for OUD. Along with taking a range of safety measures, efficacy for cue-induced craving was evaluated prior to (Day 1) and following (Day 19) treatment using a Visual Analogue Scale (VAS) in response to a cue reactivity task during functional near-infrared spectroscopy (fNIRS) and for craving. Efficacy of treatment for ambient craving was assessed using Ecological Momentary Assessment (EMA) prior to (Study Day 1), across (Study Days 2-19), and following (Study Days 20-21) residential treatment. DISCUSSION: This manuscript describes a protocol to collect clinical data on the safety and efficacy of a GLP-1RA, liraglutide, during residential treatment of persons with OUD, laying the groundwork for further evaluation in a larger, outpatient OUD population. Improved understanding of innovative, non-opioid based treatments for OUD will have the potential to inform community-based interventions and health policy, assist physicians and health care professionals in the treatment of persons with OUD, and to support individuals with OUD in their effort to live a healthy life. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04199728. Registered 16 December 2019, https://clinicaltrials.gov/study/NCT04199728?term=NCT04199728 . PROTOCOL VERSION: 10 May 2023.

Familial aggregation of circulating C-reactive protein in polycystic ovary syndrome.

STUDY QUESTION: What is the heritability of C-reactive protein (CRP) levels in women with polycystic ovary syndrome (PCOS) and their first-degree relatives? SUMMARY ANSWER: Women with PCOS and their siblings are more likely to have elevated CRP levels when both of their parents have elevated CRP. This PCOS family-based study indicates that CRP levels are likely a heritable trait. WHAT IS KNOWN ALREADY: Previous studies have established that an elevated blood level of CRP is variably present in women with PCOS, and may be present independent of metabolic status. STUDY DESIGN, SIZE AND DURATION: A familial based phenotyping study consisting of 81 families comprised of PCOS patients and their first-degree relatives for 305 subjects. PARTICIPANTS/MATERIALS, SETTING AND METHODS: Study conducted at an academic health center. An elevated CRP level was defined as >28.6 nmol/l. To account for familial clustering, generalized estimating equations with a logit link were used to model the association between elevated CRP levels in patients with PCOS and their siblings with their parental group (A = neither parent with elevated CRP; B = one parent with elevated CRP; C= both parents with elevated CRP), adjusting for gender, age and BMI of the offspring. We did additional heritability analyses by using a variance component estimation method for CRP levels, adjusting for sex, age and BMI. MAIN RESULTS AND THE ROLE OF CHANCE: We observed elevated CRP levels in 94% of the offspring in group C, 45% in group B and 10% in group A after adjusting for age, gender and BMI of the offspring. The median BMI of the offspring in group A, B and C were 30.0, 28.7 and 31.2 kg/m², respectively. Heritability estimates of CRP levels ranged from 0.75 to 0.83 and remained significant after excluding for type 2 diabetes mellitus. Our small sample size increases the possibility of a type 1 error. LIMITATIONS, REASONS FOR CAUTION: This is a single report in an adequately powered but limited sample size study identifying the strong heritability of CRP levels. Replication in other large family cohorts is necessary. WIDER IMPLICATION OF THE FINDINGS: These findings support the concept that there is an increased cardiovascular disease risk profile in families of women with PCOS. STUDY FUNDING/COMPETING INTEREST: This research was supported by National Institutes of Health grants U54HD-034449 and P50 HD044405 (A.D.). Priyathama Vellanki is supported in part by NIH/NIDDK Training Grant T32 DK007169.

Spontaneous secondary pneumothorax due to cannabis-induced bullous lung disease: a case report.

Marijuana use has grown rapidly in the last decade with a prevalence greater than that of cocaine and opioids. With its increasing recreational and medical use, potential adverse outcomes from heavy use may be associated with bullous lung disease and spontaneous pneumothorax. This case report has been reported in line with the SCARE Criteria. Case presentation: The authors describe a case of an adult male with a past medical history of spontaneous pneumothorax and long-standing marijuana use presenting with dyspnoea who was found to have a secondary spontaneous pneumothorax requiring invasive treatment. Clinical discussion: The aetiology of lung injury due to heavy marijuana smoke may be from direct tissue injury from inhaled irritants and the method of which marijuana smoke is inhaled compared with tobacco smoke. Conclusion: Chronic marijuana use should be considered when evaluating structural lung disease and pneumothorax in the setting of minimal tobacco use.

(2Z)-N-(2-Chloro-benz-yl)-2-(2-oxo-2,3-dihydro-1H-indol-3-yl-idene)hydrazinecarbothio-amide.

In the title compound, C(16)H(13)ClN(4)OS, the isatin ring system is oriented at dihedral angles of 10.60 (7) and 72.60 (3)° with respect to the thio-semicarbazide and 2-chloro-benzyl groups, respectively. The near planarity of the isatin and thio-semicarbazide groups [r.m.s. deviations of 0.0420 and 0.0163 Å, respectively] is reinforced by intra-molecular N-H⋯O and N-H⋯N hydrogen bonds, which generate S(6) and S(5) rings, respectively. In the crystal, inversion dimers linked by pairs of N-H⋯O hydrogen bonds generate R(2) (2)(8) loops. Aromatic π-π stacking inter-actions between the centroids of heterocyclic five-membered and benzene rings [distance = 3.6866 (11) Å] are also observed.

Paroxysmal nocturnal hemoglobinuria clone in a patient with acute promyelocytic leukemia.

Acute promyelocytic leukemia (APL) is a unique subtype of acute myeloid leukemia (AML), which presents with a distinct coagulopathy. Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hemolytic anemia which is clonal in nature due to somatic mutation. PNH may evolve to aplastic anemia, and more rarely, to a myelodysplastic syndrome or to AML. The literature review showed that AML is derived from the PNH clone as the leukemic cells lack the expression of glycosylphosphatidylinositol-linked proteins and PNH phenotype disappeared with the onset of acute leukemia. Herein, we report an unusual presentation of the coexistence of two clonal disorders PNH and APL. Our case contributes to the literature that AML in the setting of PNH is a separate disorder.