Widespread posttranscriptional regulation of cotransmission.

While neurotransmitter identity was once considered singular and immutable for mature neurons, it is now appreciated that one neuron can release multiple neuroactive substances (cotransmission) whose identities can even change over time. To explore the mechanisms that tune the suite of transmitters a neuron releases, we developed transcriptional and translational reporters for cholinergic, glutamatergic, and GABAergic signaling in Drosophila. We show that many glutamatergic and GABAergic cells also transcribe cholinergic genes, but fail to accumulate cholinergic effector proteins. Suppression of cholinergic signaling involves posttranscriptional regulation of cholinergic transcripts by the microRNA miR-190; chronic loss of miR-190 function allows expression of cholinergic machinery, reducing and fragmenting sleep. Using a "translation-trap" strategy, we show that neurons in these populations have episodes of transient translation of cholinergic proteins, demonstrating that suppression of cotransmission is actively modulated. Posttranscriptional restriction of fast transmitter cotransmission provides a mechanism allowing reversible tuning of neuronal output.

Widespread post-transcriptional regulation of co-transmission.

While neurotransmitter identity was once considered singular and immutable for mature neurons, it is now appreciated that one neuron can release multiple neuroactive substances (co-transmission) whose identities can even change over time. To explore the mechanisms that tune the suite of transmitters a neuron releases, we developed transcriptional and translational reporters for cholinergic, glutamatergic, and GABAergic signaling in Drosophila . We show that many glutamatergic and GABAergic cells also transcribe cholinergic genes, but fail to accumulate cholinergic effector proteins. Suppression of cholinergic signaling involves posttranscriptional regulation of cholinergic transcripts by the microRNA miR-190; chronic loss of miR-190 function allows expression of cholinergic machinery, reducing and fragmenting sleep. Using a "translation-trap" strategy we show that neurons in these populations have episodes of transient translation of cholinergic proteins, demonstrating that suppression of co-transmission is actively modulated. Posttranscriptional restriction of fast transmitter co-transmission provides a mechanism allowing reversible tuning of neuronal output. One-Sentence Summary: Cholinergic co-transmission in large populations of glutamatergic and GABAergic neurons in the Drosophila adult brain is controlled by miR-190.

Mechanistic Modelling of Biomass Growth, Glucose Consumption and Ethanol Production by Kluyveromyces marxianus in Batch Fermentation.

This paper presents results concerning mechanistic modeling to describe the dynamics and interactions between biomass growth, glucose consumption and ethanol production in batch culture fermentation by Kluyveromyces marxianus (K. marxianus). The mathematical model was formulated based on the biological assumptions underlying each variable and is given by a set of three coupled nonlinear first-order Ordinary Differential Equations. The model has ten parameters, and their values were fitted from the experimental data of 17 K. marxianus strains by means of a computational algorithm design in Matlab. The latter allowed us to determine that seven of these parameters share the same value among all the strains, while three parameters concerning biomass maximum growth rate, and ethanol production due to biomass and glucose had specific values for each strain. These values are presented with their corresponding standard error and 95% confidence interval. The goodness of fit of our system was evaluated both qualitatively by in silico experimentation and quantitative by means of the coefficient of determination and the Akaike Information Criterion. Results regarding the fitting capabilities were compared with the classic model given by the logistic, Pirt, and Luedeking-Piret Equations. Further, nonlinear theories were applied to investigate local and global dynamics of the system, the Localization of Compact Invariant Sets Method was applied to determine the so-called localizing domain, i.e., lower and upper bounds for each variable; whilst Lyapunov's stability theories allowed to establish sufficient conditions to ensure asymptotic stability in the nonnegative octant, i.e., R+,03. Finally, the predictive ability of our mechanistic model was explored through several numerical simulations with expected results according to microbiology literature on batch fermentation.

ß-Hydroxyphosphocarnitine modifies fibrosis, steatosis and improves liver function in non-alcoholic steatohepatitis induced in rats.

BACKGROUND: Non-alcoholic steatohepatitis (NASH) is a chronic disease characterized by inflammation, steatosis, and liver fibrosis. The liver is particularly affected by alterations in lipid metabolism. Our aim was to evaluate the effect of ß-hydroxyphosphocarnitine (ß-HPC) on NASH induced in rats. METHODS: NASH was produced via the ad libitum daily chronic administration of a fructose solution (400 kcal) for 9 weeks, an oral dose of fat solution (16 kcal) for 7 weeks and a subcutaneous injection of CCl4 (30%) two times a week for 2 weeks to Wistar rats. To evaluate the effect of ß-HPC, a dose of 100 mg/kg was administered perorally for 4 weeks and its biochemical and hepatic effects on rats with NASH were analyzed. Serum levels of glucose, triglycerides, cholesterol, and liver enzymes were quantified. Histological changes were evaluated on slices stained with H&E, trichromic and PAS. Glycogen content was measured in liver samples. α-SMA and SREBP-1 immunopositive cells were identified in liver tissue. RESULTS: NASH was characterized by elevated triglycerides, elevated liver damage enzymes, and the presence of necrosis, inflammation, steatosis, and fibrosis. Significant amounts of glycogen were found, along with α-SMA positive cells in fibrosis areas. The over-expression of SREBP-1 in cytoplasm and nuclei was evident. Animals with NASH treated with ß-HPC showed a significant reduction in inflammation, necrosis, and glycogen content in the liver. A reduction in α-SMA and SREBP-1 immunopositive cells correlated with a significant reduction in the degree of fibrosis and steatosis found in liver tissue. ß-HPC reduced the levels of ALP and GGT, and significantly reduced triglyceride levels. Animals treated with ß-HPC did not show any alterations in liver enzyme function. CONCLUSIONS: Our research shows that ß-HPC can improve liver function and morphology in the case of NASH induced in rats, suggesting ß-HPC could be potentially used in the treatment of NASH.

The Drosophila microRNA bantam regulates excitability in adult mushroom body output neurons to promote early night sleep.

Sleep circuitry evolved to have both dedicated and context-dependent modulatory elements. Identifying modulatory subcircuits and understanding their molecular machinery is a major challenge for the sleep field. Previously, we identified 25 sleep-regulating microRNAs in Drosophila melanogaster, including the developmentally important microRNA bantam. Here we show that bantam acts in the adult to promote early nighttime sleep through a population of glutamatergic neurons that is intimately involved in applying contextual information to behaviors, the γ5ß'2a/ß'2mp/ß'2mp_bilateral Mushroom Body Output Neurons (MBONs). Calcium imaging revealed that bantam inhibits the activity of these cells during the early night, but not the day. Blocking synaptic transmission in these MBONs rescued the effect of bantam knockdown. This suggests bantam promotes early night sleep via inhibition of the γ5ß'2a/ß'2mp/ß'2mp_bilateral MBONs. RNAseq identifies Kelch and CCHamide-2 receptor as possible mediators, establishing a new role for bantam as an active regulator of sleep and neural activity in the adult fly.

Multicomponent Reactions for the Synthesis of Active Pharmaceutical Ingredients.

Multicomponent reactions 9i.e., those that engage three or more starting materials to form a product that contains significant fragments of all of them), have been widely employed in the construction of compound libraries, especially in the context of diversity-oriented synthesis. While relatively less exploited, their use in target-oriented synthesis offers significant advantages in terms of synthetic efficiency. This review provides a critical summary of the use of multicomponent reactions for the preparation of active pharmaceutical principles.

A comparison assessment of landfill waste incineration and methane capture in the central region of Mexico.

This article aims to conduct a techno-economic feasibility assessment of producing energy by waste incineration and methane capture in the central region of Mexico. Three scenarios at different efficiency rates were considered: 50, 80 and 100%. For the methane project, yields and power capacity were determined using the potential generation rate and the degradable organic carbon content through the LandGEM model. For incineration, the waste calorific potential and the average moisture content were used to estimate the achievable electrical performance. The estimated annual energy was 35,018 GWh for methane, compared to 537.71 GWh for incineration. Both projects reported financial economic feasibilities when evaluated at a discount rate of 12%. Incineration reported an net present value of US$49,942,534 and an internal rate of return of 26% in contrast to US$4,054,109 and 17% for the methane project. Although the payback period for incineration was lower than for methane, its levelized cost of energy was significantly higher. These results are intended to assist the decision-making process when planning and developing waste management strategies under principles of circular economy in Mexico and similar regions worldwide.

A Course Design for Remote Teaching Advanced Topics in Neuroscience.

The COVID-19 pandemic pushed educators to engage in remote teaching out of necessity, but as our relationship with teaching technology grows, remote teaching has emerged as a suitable substitute for in-person education. In this manuscript, we detail a course design for remote teaching advanced topics in neuroscience at the undergraduate level. The course and its different features were designed to fulfill a set of learning goals that closely align with those put forth by the Faculty for Undergraduate Neuroscience (FUN) and the American Association for the Advancement of Science (AAAS). Furthermore, these learning goals can be applied to any advanced neuroscience class, regardless of the topic material. To achieve these goals, we created a curriculum with distinct design features. These features included a synchronous lecture-discussion system, asynchronous lesson content videos, guest principal investigators, and deemphasized grading. Instead of traditional examination, the students participated in assignments designed to give them extensive science communication experience. At the end of the course, we indirectly assessed student outcomes using an Instructor Course Evaluation survey distributed by the university. From this survey, we were able to conclude that students' perception of the final course outcome was highly satisfactory, with strong indications that the students believed we met our learning goals. Thus, the course design described herein represents a tool for others wishing to utilize it for remote teaching advanced topics in science.

The Role of Colony Temperature in the Entrainment of Circadian Rhythms of Honey Bee Foragers.

Honey bees utilize their circadian rhythms to accurately predict the time of day. This ability allows foragers to remember the specific timing of food availability and its location for several days. Previous studies have provided strong evidence toward light/dark cycles being the primary Zeitgeber for honey bees. Work in our laboratory described large individual variation in the endogenous period length of honey bee foragers from the same colony and differences in the endogenous rhythms under different constant temperatures. In this study, we further this work by examining the temperature inside the honey bee colony. By placing temperature and light data loggers at different locations inside the colony we measured temperature at various locations within the colony. We observed significant oscillations of the temperature inside the hive, that show seasonal patterns. We then simulated the observed temperature oscillations in the laboratory and found that using the temperature cycle as a Zeitgeber, foragers present large individual differences in the phase of locomotor rhythms for temperature. Moreover, foragers successfully synchronize their locomotor rhythms to these simulated temperature cycles. Advancing the cycle by six hours, resulting in changes in the phase of activity in some foragers in the assay. The results are shown in this study highlight the importance of temperature as a potential Zeitgeber in the field. Future studies will examine the possible functional and evolutionary role of the observed phase differences of circadian rhythms.

Status of the neuromyelitis optica spectrum disorder in Latin America.

BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSD) is an increasing diagnostic and therapeutic challenge in Latin America (LATAM). Despite the heterogeneity of this population, ethnic and socioeconomic commonalities exist, and epidemiologic studies from the region have had a limited geographic and population outreach. Identification of some aspects from the entire region are lacking. OBJECTIVES: To determine ethnic, clinical characteristics, and utilization of diagnostic tools and types of therapy for patients with NMOSD in the entire Latin American region. METHODS: The Latin American Committee for Treatment and Research in MS (LACTRIMS) created an exploratory investigational survey addressed by Invitation to NMOSD Latin American experts identified through diverse sources. Data input closed after 30 days from the initial invitation. The questionnaire allowed use of absolute numbers or percentages. Multiple option responses covering 25 themes included definition of type of practice; number of NMOSD cases; ethnicity; utilization of the 2015 International Panel criteria for the diagnosis of Neuromyelitis optica (IPDN); clinical phenotypes; methodology utilized for determination of anti-Aquaporin-4 (anti- AQP4) antibodies serological testing, and if this was performed locally or processed abroad; treatment of relapses, and long-term management were surveyed. RESULTS: We identified 62 investigators from 21 countries reporting information from 2154 patients (utilizing the IPDN criteria in 93.9% of cases), which were categorized in two geographical regions: North-Central, including the Caribbean (NCC), and South America (SA). Ethnic identification disclosed Mestizos 61.4% as the main group. The most common presenting symptoms were concomitant presence of optic neuritis and transverse myelitis in 31.8% (p=0.95); only optic neuritis in 31.4% (more common in SA), p<0.001); involvement of the area postrema occurred in 21.5% and brain stem in 8.3%, both were more frequent in the South American cases (p<0.001). Anti-AQP4 antibodies were positive in 63.9% and anti-Myelin Oligodendrocyte Glycoprotein (MOG) antibodies in 4.8% of total cases. The specific laboratorial method employed was not known by 23.8% of the investigators. Acute relapses were identified in 81.6% of cases, and were treated in 93.9% of them with intravenous steroids (IVS); 62.1% with plasma exchange (PE), and 40.9% with intravenous immunoglobulin-G (IVIG). Therapy was escalated in some cases due to suboptimal initial response. Respondents favored Rituximab as long-term therapy (86.3%), whereas azathioprine was also utilized on 81.8% of the cases, either agent used indistinctly by the investigators according to treatment accessibility or clinical judgement. There were no differences among the geographic regions. CONCLUSIONS: This is the first study including all countries of LATAM and the largest cohort reported from a multinational specific world area. Ethnic distributions and phenotypic features of the disease in the region, challenges in access to diagnostic tools and therapy were identified. The Latin American neurological community should play a determinant role encouraging and advising local institutions and health officials in the availability of more sensitive and modern diagnostic methodology, in facilitating the the access to licensed medications for NMOSD, and addressing concerns on education, diagnosis and management of the disease in the community.

Molecular characterization of KPC-2-producing Klebsiella pneumoniae ST258 isolated from bovine mastitis.

Bovine mastitis, an inflammation of the mammary gland of dairy cattle, is the most prevalent disease causing economically important losses, reduced milk production, early culling, veterinary expenses, and higher death rates. Bovine mastitis infections are the main cause for the use of antibiotics; however, the emergence of multidrug-resistant bacteria and the poor or nil response to antibiotics has become a critical global health problem. The goal of this study was the characterization of bacterial infections associated with clinical bovine mastitis. All the isolates were multidrug-resistant and were negative for the production of extended spectrum ß-lactamases. However, all isolates were identified as carbapenemase-producing organisms by the Carba NP test. The carbapenemase identified was the product of the KPC-2 gene. The isolates were identified as Klebsiella pneumoniae and contained virulence genes for fimbriae, lipopolysaccharides, nitrogen starvation genes, and siderophores. Sixty-nine percent of the KPC-2-producing isolates had the same plasmid profile, although the genetic mobilization of resistance by bacterial conjugation was unsuccessful. The carbapenemase corresponded to the plasmid-borne KPC-2 gene identified by Southern blot hybridization. The assay showed a positive signal in the 90 kb (69% of the isolates), 165 kb (31% of the isolates), and 130 kb (6% of the isolates) plasmids. The IncFIIy and IncFIIk replicons were detected among these K. pneumoniae isolates. The PFGE and MLST analysis showed that all of the isolates are comprised by two clones (A and B) belonging to Sequence Type 258. This is the first report of K. pneumoniae producing carbapenemase KPC-2 isolated from bovine mastitis.

Regulation of Olfactory Associative Memory by the Circadian Clock Output Signal Pigment-Dispersing Factor (PDF).

Dissociation between the output of the circadian clock and external environmental cues is a major cause of human cognitive dysfunction. While the effects of ablation of the molecular clock on memory have been studied in many systems, little has been done to test the role of specific clock circuit output signals. To address this gap, we examined the effects of mutations of Pigment-dispersing factor (Pdf) and its receptor, Pdfr, on associative memory in male and female Drosophila Loss of PDF signaling significantly decreases the ability to form associative memory. Appetitive short-term memory (STM), which in wild-type (WT) is time-of-day (TOD) independent, is decreased across the day by mutation of Pdf or Pdfr, but more substantially in the morning than in the evening. This defect is because of PDFR expression in adult neurons outside the core clock circuit and the mushroom body (MB) Kenyon cells (KCs). The acquisition of a TOD difference in mutants implies the existence of multiple oscillators that act to normalize memory formation across the day for appetitive processes. Interestingly, aversive STM requires PDF but not PDFR, suggesting that there are valence-specific pathways downstream of PDF that regulate memory formation. These data argue that the circadian clock uses circuit-specific and molecularly diverse output pathways to enhance the ability of animals to optimize responses to changing conditions.SIGNIFICANCE STATEMENT From humans to invertebrates, cognitive processes are influenced by organisms' internal circadian clocks, the pace of which is linked to the solar cycle. Disruption of this link is increasingly common (e.g., jetlag, social jetlag disorders) and causes cognitive impairments that are costly and long lasting. A detailed understanding of how the internal clock regulates cognition is critical for the development of therapeutic methods. Here, we show for the first time that olfactory associative memory in Drosophila requires signaling by Pigment-dispersing factor (PDF), a neuromodulatory signaling peptide produced only by circadian clock circuit neurons. We also find a novel role for the clock circuit in stabilizing appetitive sucrose/odor memory across the day.

Clinical translation of a PSMA inhibitor for 99mTc-based SPECT.

BACKGROUND: Prostate-specific membrane antigen (PSMA) is highly over-expressed in advanced prostate cancers. 68Ga-labeled PSMA inhibitors (iPSMA) are currently used for prostate cancer detection by PET imaging. The availability of simple, efficient and reproducible radiolabeling procedures is essential for developing new SPECT radiopharmaceuticals for clinical translation. The aim of this research was to prepare 99mTc-EDDA/HYNIC-Lys(Nal)-Urea-Glu (99mTc-EDDA/HYNIC-iPSMA) obtained from lyophilized kit formulations and evaluate the in vitro and in vivo radiopharmaceutical binding to prostate cancer cells over-expressing PSMA, as well as the 99mTc-EDDA/HYNIC-iPSMA normal biodistribution in humans and the preliminary uptake in patients with prostate cancer. METHODS: 99mTc labeling was performed by adding sodium pertechnetate solution and a 0.2M phosphate buffer (pH 7.0) to a lyophilized formulation containing HYNIC-iPSMA, EDDA, tricine, mannitol and stannous chloride. The radiochemical purity was evaluated by reversed-phase HPLC and ITLC-SG analyses. Stability studies in human serum were performed by size-exclusion HPLC. In vitro cell uptake was tested using prostate cancer cells (LNCaP) with blocked and non-blocked receptors. Biodistribution and tumor uptake were determined in LNCaP tumor-bearing nude mice with blocked and non-blocked receptors, and images were obtained using a micro-SPECT/CT. Whole-body images from three healthy men and two patients with histologically-confirmed prostate cancer (one of them with a previous 68Ga-PSMA-617scan) were acquired at 1h and 3h after 99mTc-EDDA/HYNIC-iPSMA administration with radiochemical purities of >98%. RESULTS: In vitro and in vivo studies showed high radiopharmaceutical stability in human serum, specific recognition for PSMA, high tumor uptake (10.22±2.96% ID/g at 1h) with rapid blood clearance and mainly kidney elimination. Preliminary images in patients demonstrated the ability of 99mTc-EDDA/HYNIC-iPSMA to detect tumors and metastases of prostate cancer as well as 68Ga-PSMA-617 does. CONCLUSIONS: The results obtained in this study warrant further dosimetry and clinical studies to determine the specificity and sensitivity of 99mTc-EDDA/HYNIC-iPSMA.

Two Novel Nanosized Radiolabeled Analogues of Somatostatin for Neuroendocrine Tumor Imaging.

The somatostatin receptors (SR), which are overexpressed in a majority of neuroendocrine tumors, are targets for radiopeptide-based imaging using for example the 99mTc-Tyr3-Octreotide peptide. Dendrimers are hyperbranched polymeric structures. The nanoscopic size and near-monodisperse nature properties give polyamidoamine (PAMAM) dendrimers an edge over linear polymers in the context of drug delivery. Gold nanoparticles (AuNPs) conjugated to peptides produces stable multimeric systems with target-specific molecular recognition. The aim of this research was to prepare two nanosized multimeric systems for neuroendocrine tumor imaging, 99mTc-PAMAM-Tyr3-Octreotide and 99mTc-AuNP-Tyr-Octreotide, and to compare their in vitro uptake in SR-positive AR42J cancer cells as well as their biodistribution profile in athymic mice bearing AR42J tumors. [Tyr3, Lys(Boc)5]-Octreotide was conjugated to the carboxylate groups of the PAMAM dendrimer (G3.5) with further Boc deprotection using TFA. 99mTc labeling was carried out by a direct method. 99mTc-Tyr3-Octreotide was conjugated to AuNPs (20 nm) by spontaneous reaction with the thiol group of cysteine. Radiochemical purity (RP) was determined by size-exclusion HPLC and ITLC-SG analyses. In vitro binding studies were carried out in AR42J cancer cells. Biodistribution studies were accomplished in athymic mice with AR42J-induced tumors with blocked and unblocked receptors. Elemental analysis demonstrated that 26 Tyr3-Octreotide molecules were successfully conjugated to one molecule of PAMAM. RP for both nanosized conjugates was > 94% and showed recognition for SR in AR42J cells. The tissue distribution of radioactivity 2 h after 99mTc-PAMAM-Tyr3-Octreotide administration in mice showed specific tumor uptake (4.12 ± 0.57% of injected dose/g) and high accumulation in the pancreas (15.08 ± 3.11% of injected dose/g) which expresses SR. No significant difference in the tumor uptake was found between 99mTc-PAMAM-Tyr3-Octreotide and 99mTc-AuNP-Tyr3-Octreotide. However, the dendrimer-peptide conjugate showed a significant renal excretion. Both radiopharmaceuticals demonstrated properties suitable for use as target-specific agents for molecular imaging of tumors that overexpressed SR.

Idiopathic CD4+ lymphocytopenia in Hispanic male: case report and literature review.

INTRODUCTION: Idiopathic cluster of differentiation 4 (CD4+) T-cell lymphocytopenia (ICL) is a rare non human immunodeficiency virus (HIV)-related syndrome with unclear natural history and prognosis that was first reported and defined in 1992. ICL has been observed in patients after the onset of an opportunistic infection without known immunosuppression. CASE PRESENTATION: A 20-year-old Hispanic male patient without significant past medical history presented with progressive shortness of breath and cough for 3 weeks. Chest computed tomography showed bilateral cavitary lesions in the upper lung lobes. The HIV rapid screening test as well as the sputum acid-fast bacilli test were both positive. The patient was started on antituberculosis therapy. The CD4 count was noticed to be low. However, the HIV Western blot test was negative, and the HIV viral load was within normal limit. Further radiologic studies, hemato-oncologic, and autoimmune workups were normal. The patient was discharged on the treatment for tuberculosis. Follow-up after 8 weeks revealed a persistent low CD4+ count, and the repeated HIV tests were negative. CONCLUSION: The clinical features of ICL range from an asymptomatic condition to life-threatening complications that imitate the clinical course of HIV-infected patients. The differential diagnosis in adults comprises primarily HIV infection and other diseases or drug side effects. ICL is very rare and should be considered in the absence of any defined immunodeficiency or therapy associated with depressed levels of CD4+ T-cells. Early detection and recognition of the disease allow purposeful and systemic treatment approach and screening for the affected patients.

Chorea, Hyperglycemia, Basal Ganglia Syndrome (C-H-BG) in an uncontrolled diabetic patient with normal glucose levels on presentation.

PATIENT: Female, 66 FINAL DIAGNOSIS: Chorea • hyperglycemia • Basal Ganglia Syndrome (C-H-BG) Symptoms: Hemibalism • hemichorea MEDICATION: - Clinical Procedure: - Specialty: Endocrinology and Metabolic. OBJECTIVE: Challenging differential diagnosis. BACKGROUND: Hemichorea-hemiballism (HCHB) is a spectrum of involuntary, continuous non-patterned movement involving 1 side of the body. Possible causes of HCHB include hemorrhagic or ischemic stroke, neoplasm, systemic lupus erythematosus, HHNK, Wilson's disease, and thyrotoxicosis. This case illustrates the need to be aware of hyperglycemia as a cause of hemiballism/hemichorea, which is now referred to in the medical literature as C-H-BG (chorea, hyperglycemia, basal ganglia) syndrome. CASE REPORT: A 66-year-old Hispanic woman presented to our care with hemiballism/hemichorea of the right arm and leg of 1 week duration. She had been admitted 3 months prior with toxic metabolic encephalopathy secondary to hyperosmolar hyperglycemic non-ketotic syndrome with a blood glucose level of 984 mg/dL. Her blood glucose level was normal but hemoglobin A1C was 12.2%. A brain MRI revealed an asymmetric T1 hyperintensity of the left putamen. This specific finding was compatible with hyperglycemia-induced hemichorea hemiballism syndrome. The hemiballism/hemichorea slowly improved over the course of the hospitalization with strict glycemic control. At the 3-month follow-up visit she had no involuntary movements of her extremities, and she had well controlled blood glucose levels and a hemoglobin A1C of 9.0. CONCLUSIONS: In a patient with normal glycemic levels but a history of uncontrolled diabetes, C-H-BG syndrome should be on the top of the differential list when the characteristic MRI findings of a hyperintensity in the basal ganglia are observed. This is a rare disease that deserves attention because it is reversible with correction of hyperglycemia. Thus, prompt recognition and treatment is essential to avoid adverse outcomes.

Dilated cardiomyopathy secondary to chronic cocaine abuse: a case report.

BACKGROUND: Cocaine is a potent sympathomimetic agent associated with the development of possible fatal cardiovascular complications. Dysrhythmias, acute myocardial infarction, hypertension and dilated cardiomyopathy are just some of many cardiovascular effects related to the abuse of cocaine. CASE PRESENTATION: A 38-year-old Hispanic male with a past medical history of hypertension presented with a chief complaint of progressive shortness of breath. The patient confessed to the use of cocaine for almost 18 years once per week. On examination he was hypertensive and tachycardic with a systolic murmur over the 5th intercostal space at the level of the left mid-clavicular line. Laboratory workup revealed an elevated Brain natriuretic peptide; urine toxicology was positive for cocaine. 2D-echocardiogram showed dilated cardiomyopathy. Cardiac catheterization excluded angioischemic cause. He was managed medically and subsequently discharged with drug rehabilitation. On follow-up diagnostic evaluation after 5 months of cocaine cessation, his ejection function improved significantly. CONCLUSION: The exact incidence of cocaine related cardiomyopathy is unknown and likely underreported. The clinical course is abrupt and comparatively similar to other types of cardiomyopathy. The management is like other forms of cardiomyopathy; however ß-blockers should be avoided. The myocardial dysfunction is reversible with abstaining from additional cocaine ingestion. Non-invasive testing should be performed after several months to re-evaluate the treatment response.

Biventricular non-compaction with predominant right ventricular involvement, reduced left ventricular systolic and diastolic function, and pulmonary hypertension in a Hispanic male.

PATIENT: Male, 22 FINAL DIAGNOSIS: Cardiomyopathy Symptoms: Shortness of breath • dispnoea • chest discomfort MEDICATION: - Clinical Procedure: Echocardiogram • cardiac MRI Specialty: Cardiology. OBJECTIVE: Challenging differential diagnosis. BACKGROUND: Non-compaction cardiomyopathy (NCM) is a rare congenital cardiomyopathy characterized by increased trabeculation in one or more segments of the ventricle. The left ventricle is most commonly affected. However, biventricular involvement or right ventricle predominance has also been described. Clinical features of NCM are non-specific and can range from being asymptomatic to symptoms of congestive heart failure, arrhythmia, and systemic thromboembolism. CASE REPORT: 22-year-old Hispanic male presented with two month history of chest discomfort. Laboratory workup revealed an elevated brain-natriuretic-peptide of 1768 pg/ml. ECG and chest x-ray was nonspecific. Transthoracic echocardiogram revealed prominent trabeculae and spongiform appearance of the left ventricle (LV) with an ejection-fraction of 15-20%; 5 of 9 segments of the LV were trabeculated with deep intertrabecular recesses also involving the right ventricle (RV) with demonstrated blood flow in these recesses on color-doppler. The biventricular spongiform appearance was morphologically suggestive for NCM with involvement of the RV. Confirmatory cardiac MRI was performed, demonstrating excessive trabeculation of the left-ventricular apex and mid-ventricular segments. Hypertrabecularion was exhibited at the apical and lateral wall of the RV. Cardiac catheterization showed an intact cardiac vessel system. The patient was discharged on heart failure treatment and was placed on the heart transplantation list. CONCLUSIONS: NCM is a unique disorder resulting in serious and severe complications. The majority of the reported cases describe the involvement of the left ventricle. However, the right ventricle should be taken into careful consideration. The early diagnosis may help to increase the event-free survival.