Suicide Attempt in a Poststroke Patient After Undergoing Deep Brain Stimulation: A Case Report.

Deep brain stimulation (DBS) is a type of therapy involving electrical stimulation of the brain and is primarily used to treat movement disorders. While perhaps beneficial, DBS has also been shown to have some potential major side effects, including increased risk for depression and suicide. In the present article, we report a case of a suicide attempt in a depressed patient two months after undergoing DBS for treatment of acute dystonia the patient had suffered from a prior ischemic stroke. This manuscript serves as a reminder of the negative ramifications that can be associated with DBS and why we should be cautious in providing DBS to patients who are either currently depressed or have a history of depression.

Vitamin D/Bone Mineral Density and Triglyceride Paradoxes Seen in African Americans: A Cross-Sectional Study and Review of the Literature.

Vitamin D is known to have a positive effect on bone health. Despite the greater frequency of vitamin D deficiency in African Americans (AA), they have a higher bone mineral density (BMD) compared to whites, demonstrating a disconnect between BMD and vitamin D levels in AA. Another intriguing relationship seen in AA is the triglyceride (TG) paradox, an unusual phenomenon in which a normal TG status is observed even when patients house conditions known to be characterized by high TG levels, such as Type II diabetes. To the best of our knowledge, no study has examined whether these two paradoxical relationships exist simultaneously in AA subjects with Type II diabetes. In this study, we compared levels of blood markers, including HbA1c, TG, and vitamin D, measured as serum 25-hydroxyvitamin D [25(OH)VD] µM/mL, [25(OH)VD]/TG, calcium, and BMD in AA (n = 56) and white (n = 26) subjects with Type II diabetes to see whether these relationships exist concurrently. We found that AA subjects had significantly lower TG and [25(OH)VD] levels and a significantly higher BMD status compared to white subjects, even when the ages, BMI, duration of diabetes, HbA1c, and calcium levels were similar between the two groups. This demonstrates that these two paradoxical relationships exist simultaneously in Type II diabetic AA subjects. In addition to these findings, we discuss the current hypotheses in the literature that attempt to explain why these two intriguing relationships exist. This review also discusses four novel hypotheses, such as altered circulating levels and the potential role of estrogen and hydrogen sulfide on BMD and HMG-CoA reductase as a possible contributor to the TG paradox in AA subjects. This manuscript demonstrates that there are still many unanswered questions regarding these two paradoxical relationships and further research is needed to determine why they exist and how they can be implemented to improve healthcare.

Alzheimer's Disease: A Review of Pathology, Current Treatments, and the Potential Therapeutic Effect of Decreasing Oxidative Stress by Combined Vitamin D and l-Cysteine Supplementation.

Significance: Excess oxidative stress and neuroinflammation are risk factors in the onset and progression of Alzheimer's disease (AD) and its association with amyloid-ß plaque accumulation. Oxidative stress impairs acetylcholine (ACH) and N-methyl-d-aspartate receptor signaling in brain areas that function in memory and learning. Glutathione (GSH) antioxidant depletion positively correlates with the cognitive decline in AD subjects. Treatments that upregulate GSH and ACH levels, which simultaneously decrease oxidative stress and inflammation, may be beneficial for AD. Recent Advances: Some clinical trials have shown a benefit of monotherapy with vitamin D (VD), whose deficiency is linked to AD or with l-cysteine (LC), a precursor of GSH biosynthesis, in reducing mild cognitive impairment. Animal studies have shown a simultaneous decrease in ACH esterase (AChE) and increase in GSH; combined supplementation with VD and LC results in a greater decrease in oxidative stress and inflammation, and increase in GSH levels compared with monotherapy with VD or LC. Therefore, cosupplementation with VD and LC has the potential of increasing GSH, downregulation of oxidative stress, and decreased inflammation and AChE levels. Future Directions: Clinical trials are needed to determine whether safe low-cost dietary supplements, using combined VD+LC, have the potential to alleviate elevated AChE, oxidative stress, and inflammation levels, thereby halting the onset of AD. Goal of Review: The goal of this review is to highlight the pathological hallmarks and current Food and Drug Administration-approved treatments for AD, and discuss the potential therapeutic effect that cosupplementation with VD+LC could manifest by increasing GSH levels in patients. Antioxid. Redox Signal. 40, 663-678.

Development of Oligomeric Mannose-6-phosphonate Conjugates for Targeted Protein Degradation.

Lysosome targeting chimeras (LYTACs) are a new protein degradation strategy that has recently emerged. LYTACs utilize the native cell internalization process in the body to target and degrade therapeutically relevant extracellular proteins via the lysosomal pathways. The first lysosomal internalization receptor recently used for LYTACs is the mannose-6-phosphate receptor (M6PR). M6PR is expressed across most cell types, making it ideal for internalization and degradation of numerous extracellular proteins. Herein, we report the development of a series of structurally well-defined mannose-6-phosphonate (M6Pn)-peptide conjugates that are capable of linking to a variety of targeting ligands for proteins of interest and successfully internalizing and degrading those proteins through M6PR. This will greatly facilitate the development of M6Pn based LYTACs for therapeutic applications.

Paraganglioma in a Young Adult Female Patient: A Case Report.

Paragangliomas are catecholamine-secreting neuroendocrine tumors that originate from the chromaffin cells of the sympathetic ganglia. Roughly 10% of paragangliomas are malignant, resulting in a rare occurrence of 90-95 cases per 400 million people. Herein, we report a case of a 29-year-old female patient who presented with nausea, vomiting, and bloating and was found to have a large left retroperitoneal tumor upon imaging. The tumor was successfully removed, and subsequent histological analysis was compatible with the presence of a paraganglioma. This case serves as a reminder that despite its rarity, paragangliomas should never be dismissed as a differential diagnosis if correlating symptoms and diagnostic findings are consistent with that of paraganglioma etiology.

Atypical Imaging Findings of Nonketotic Hyperglycemic Hemichorea: A Case Report and Review of the Literature.

Nonketotic hyperglycemic hemichorea (NH-HC) is a rare condition presenting in the clinical setting. Brain imaging plays an important role in diagnosing NH-HC, which typically shows basal ganglia changes contralateral to the side of the hemiballismus/hemichorea. Only a few articles in the literature have reported normal pertinent magnetic resonance/CT findings in patients presenting with NH-HC. To the authors' knowledge, no cases in the literature have reported basal ganglia changes solely observed on CT but not on MRI in patients presenting with NH-HC. Herein, we describe a unique case in which a CT of a patient presenting with NH-HC demonstrated basal ganglia abnormalities with negative MRI findings.

Adrenal Ganglioneuroblastoma of Adult Onset: A Literature Review.

Ganglioneuroblastomas (GNBs) are a rare subtype of neoplastic tumors that arise from the autonomic nervous system and contain both mature gangliocytes and immature neuroblasts. The primary age group affected by GNBs is the pediatric population, with less than 50 cases of adult GNBs existing in the literature. To the authors' best knowledge, only 21 cases of GNBs arising in the adrenal glands of adults have been reported. Herein we present a literature review examining the symptoms, treatment type, age, and sex of adults, and the presence of tumor metastases and calcification from the 21 cases reported in the literature.

The Positive Association of Plasma Levels of Vitamin C and Inverse Association of VCAM-1 and Total Adiponectin with Bone Mineral Density in Subjects with Diabetes.

CONTEXT: Population studies have shown a trend in decreasing vitamin C status and increasing prevalence of osteoporosis in patients with diabetes and non-diabetic people. Dietary vitamin C consumption is linked to improvement in bone mineral density (BMD) in epidemiological studies. VCAM-1 and adiponectin are known to activate osteoclasts, which increase bone loss. AIM: This study examined whether there is any association between the circulating level of vitamin C and BMD and whether the beneficial effect of vitamin C on BMD was linked to a simultaneous decrease in circulating levels of adiponectin and VCAM-1 in subjects with diabetes. METHODS: Patients with diabetes (T2D, n = 74) and age-matched non-diabetic controls (n = 26) were enrolled in this study. Fasting blood levels of glycemia, adiponectin, VCAM-1, inflammation biomarkers, and vitamin C were determined in both groups. The BMD of the lumbar spine (L1-L4), left femur, and right femur was determined using a DXA scan in subjects with diabetes. RESULTS: Patients with diabetes had lower levels of vitamin C and higher levels of VCAM-1 and inflammatory cytokines. There was a significant positive association between vitamin C blood levels and lumbar spine BMD as well as a significant negative association between total adiponectin and VCAM-1 levels with that of vitamin C and lumbar BMD in patients with diabetes. Total adiponectin and VCAM-1 also showed a negative association with BMD of both the right and left femurs. The inter-relationship among the circulating levels of vitamin C and VCAM-1 and BMD was strong and is a novel finding. CONCLUSIONS: This study reports a positive association of circulating vitamin C levels and the BMD and that the beneficial effects of vitamin C on BMD could be linked to a simultaneous lowering in circulating VCAM-1 and total adiponectin levels. Thus, dietary vitamin C consumption has potential to lower inflammation and the risk of osteoporosis in subjects with diabetes.

Successful Treatment of Catatonia: A Case Report and Review of Treatment.

Herein, we report the case of a 20-year-old Caucasian male with a previous psychiatric history of schizophreniform, autism, unspecified intellectual disorder, and past medical history of hypertension, who presented after a suicidal attempt. One month prior to admission for the suicidal attempt, the patient had mutism. While admitted, the patient showed signs of mutism, posturing, negativism, and waxy flexibility. Treatment with both aripiprazole and lorazepam was effective and reversed the patient's catatonia after low-dose titration. This case highlights the importance of reviewing patient history and presenting symptoms in the management of catatonia. Additionally, this case provides an opportunity to review the diagnostic approach and treatment type used for patients presenting with catatonia.

A Primer and Literature Review on Internal and External Retention Mechanisms for Catheter Fixation.

Although catheters are commonplace in hospital settings, there is scarce literature discussing the internal and external retention mechanisms used to aid in catheter fixation. Additionally, exact definitions and detailed information on internal and external retention mechanisms are almost non-existent in the literature. This article serves three primary purposes. The first purpose is to define internal and external catheter retention mechanisms, describe how they work, and provide examples of each that are routinely used in healthcare settings. The second goal of this paper is to provide a literature review comparing various aspects of the different types of internal and external catheter retention mechanisms discussed in the paper, including performance variance and the advantages and disadvantages of each. The third aim of this article is to provide a brief overview of catheter dislodgment, including the rates at which this occurs, the problems that can arise, and the best treatment option when this does occur.

A Sleeve-Sheath With a Coaxial Exchangeable Catheter for Palliative Evacuation of Recurrent Thoracic and Abdominal Effusions.

Herein we describe an outer cannula sleeve-sheath with a coaxially inserted exchangeable drainage catheter (SCDC) for effective evacuation of recurrent symptomatic fluid collections in the thorax and abdomen on patients in lieu of, or failed, current evacuation catheters and methods. The design is an alternative to existing commercially available devices and adds distinct enhancements with the possibility of intrathoracic or intrabdominal trans outer sleeve-sheath diagnostic or therapeutic interventions. This device aims at requiring a single invasive procedure (thoracentesis and paracentesis) while offering catheter exchange and repositioning if malfunction or malposition occurs during the patient's lifetime. The SCDC outer sheath in the subcutaneous tissues of the thorax or abdomen has built-in two antibacterial cuffs to prevent infection. At the same time, the exchangeable coaxially inserted drainage catheter is deployed over a guidewire within the thoracic or abdominal cavities. The drainage catheter has a fluid dynamic proven efficient design to facilitate drainage and can recanalize its lumen if occluded by fibrin or tissue.

Preoperative Embolization of a Delayed Femoral Metastasis of Renal Cell Carcinoma: A Case Report.

Preoperative embolization of hypervascular bone metastasis is an effective measure for reducing blood loss during open orthopedic surgery. When the clinician is experienced with the procedure, the risks of the procedure are minimal and final outcomes are typically good. In this study, we report a case of a 50-year-old female patient who presented with a delayed metastatic renal cell tumor in the left proximal femur one year after radical nephrectomy. The patient underwent an effective preoperative embolization, which resulted in a remarkable absence of bleeding and a successful response subsequent to surgical fixation.

An Atypical Presentation of West Nile Virus With Successful Treatment After Plasma Exchange and Intravenous Immunoglobulin.

West Nile (WN) disease is a relatively rare arboviral virus. Neuroinvasive cases of WN account for less than 1% of the total cases. The case described had difficult symptomatology and radical presentation, which included ascending paralysis. To date, there have been very few reports of West Nile cases that present with ascending paralysis. We describe the case of a 63-year-old white male who presented with a fever and proximal muscle weakness in the thighs and legs that rapidly worsened and ascended, eventually resulting in diaphragmatic paralysis. He was intubated after respiratory failure and given intravenous immunoglobulin and plasma exchange. The patient remained ventilated with persistent weakness. However, this improved after intravenous immunoglobulin and plasma exchange therapy. This case serves as a reminder to keep the diagnosis of WN on the differential, a primer on advanced treatments in the setting of aggressive atypical WN, and a lesson on similarly presenting diseases and distinguishing characteristics that may help rule out these diseases from WN.

Swallow Syncope Associated With Intermittent Sinus Pause and High-Degree Atrioventricular Block: A Case Report.

Swallow syncope, also known as deglutition syncope, is a relatively rare neurogenic disorder that is triggered by oral intake. When diagnosed, swallow syncope is treatable, but it is challenging to identify without proper history and prior knowledge of this disorder. Here, we describe the case of a 68-year-old female with a complex history who presented to the emergency room with complaints of worsening long-term intermittent lightheadedness and dizziness associated with swallowing. During her hospital stay, the patient was noted to have a high-degree atrioventricular block on telemetry during dinner time. A repeat electrocardiogram (ECG) demonstrated a prolonged P-R interval, and a temporal relationship between swallowing cold water and electrocardiogram (ECG) changes was demonstrated. A diagnosis of swallow syncope was confirmed. Electrophysiology was consulted and a pacemaker was placed. Symptoms of swallow-associated arrhythmias completely resolved after pacemaker implantation. This case illustrates the challenging problem of swallow syncope. While swallow syncope is highly treatable once identified, the challenge lies in identifying the disorder.

Mild Cu(OTf)2-Mediated C-Glycosylation with Chelation-Assisted Picolinate as a Leaving Group.

C-Glycosylation reactions of glycosyl picolinates with allyltrimethylsilane or silyl enol ethers were developed. Picolinate as a chelation-assisted leaving group could be activated by Cu(OTf)2 and avoided the use of harsh Lewis acids. The glycosylations were operated under mild neutral conditions and gave the corresponding C-glycosides in up to 95% yield with moderate to excellent stereoselectivities.

Chemical Synthesis and Biological Application of Modified Oligonucleotides.

RNA plays a myriad of roles in the body including the coding, decoding, regulation, and expression of genes. RNA oligonucleotides have garnered significant interest as therapeutics via antisense oligonucleotides or small interfering RNA strategies for the treatment of diseases ranging from hyperlipidemia, HCV, and others. Additionally, the recently developed CRISPR-Cas9 mediated gene editing strategy also relies on Cas9-associated RNA strands. However, RNA presents numerous challenges as both a synthetic target and a potential therapeutic. RNA is inherently unstable, difficult to deliver into cells, and potentially immunogenic by itself or upon modification. Despite these challenges, with the help of chemically modified oligonucleotides, multiple RNA-based drugs have been approved by the FDA. The progress is made possible due to the nature of chemically modified oligonucleotides bearing advantages of nuclease stability, stronger binding affinity, and some other unique properties. This review will focus on the chemical synthesis of RNA and its modified versions. How chemical modifications of the ribose units and of the phosphatediester backbone address the inherent issues with using native RNA for biological applications will be discussed along the way.

Synthesis of Glycosyl Chlorides and Bromides by Chelation Assisted Activation of Picolinic Esters under Mild Neutral Conditions.

A general method has been developed for the formation of glycosyl chlorides and bromides from picolinic esters under mild and neutral conditions. Benchtop stable picolinic esters are activated by a copper(II) halide species to afford the corresponding products in high yields with a traceless leaving group. Rare ß glycosyl chlorides are accessible via this route through neighboring group participation. Additionally, glycosyl chlorides with labile protecting groups previously not easily accessible can be prepared.