Chiffon triggers global histone H3 acetylation and expression of developmental genes in Drosophila embryos.

The histone acetyltransferase Gcn5 is critical for gene expression and development. In Drosophila, Gcn5 is part of four complexes (SAGA, ATAC, CHAT and ADA) that are essential for fly viability and have key roles in regulating gene expression. Here, we show that although the SAGA, ADA and CHAT complexes play redundant roles in embryonic gene expression, the insect-specific CHAT complex uniquely regulates expression of a subset of developmental genes. We also identify a substantial decrease in histone acetylation in chiffon mutant embryos that exceeds that observed in Ada2b, suggesting broader roles for Chiffon in regulating histone acetylation outside of the Gcn5 complexes. The chiffon gene encodes two independent polypeptides that nucleate formation of either the CHAT or Dbf4-dependent kinase (DDK) complexes. DDK includes the cell cycle kinase Cdc7, which is necessary for maternally driven DNA replication in the embryo. We identify a temporal switch between the expression of these chiffon gene products during a short window during the early nuclear cycles in embryos that correlates with the onset of zygotic genome activation, suggesting a potential role for CHAT in this process. This article has an associated First Person interview with the first author of the paper.

Effect of administration of tranexamic acid on blood loss and transfusion requirements in children undergoing posterior fossa tumor excision: a retrospective cohort study.

BACKGROUND: Surgical resection of posterior fossa tumors (PFT) in the pediatric age group often results in significant intraoperative blood loss. The primary objective was to assess the effect of tranexamic acid (TXA) on blood loss and transfusion requirement in pediatric patients undergoing excision of PFT. METHODS: In this retrospective study, all pediatric patients ≤ 18 years, who underwent PFT resection over a period of 7 years, were included. The patient and surgical characteristics, estimated blood loss (EBL), the need for blood and blood product transfusion, use of crystalloids, vasopressors, and any adverse events like seizures and thromboembolic events were recorded and compared between Group A who received TXA and Group B who did not. RESULTS: The study included 50 patients, out of which 36 belonged to Group A and 14 to Group B. The median age was 8 years (IQR, 2-17) and the mean BMI was 16.46 ± 4.11 kg/m2. The mean EBL was 224.29 ± 110.36 ml in group A (n = 36) and 362 ± 180.11 ml in group B (n = 14) (p = 0.007). The intraoperative volume of crystalloid use was significantly higher in group B (p = 0.04). The requirement of blood and blood product transfusion was similar between the groups, but the volume of blood transfusion per kg body weight was higher in group B, 8.3 (IQR, 6.7-11.1) ml/kg in Group A versus 10.5 (IQR, 8.1-16.1) ml/kg in Group B (p-value 0.3). The rates of complications noted in the form of seizures and thromboembolic events were comparable. CONCLUSION: The use of TXA in the pediatric population undergoing PFT resection aids in reducing blood loss during the surgery without increasing complications.

The interaction between the Dbf4 ortholog Chiffon and Gcn5 is conserved in Dipteran insect species.

Chiffon is the sole Drosophila ortholog of Dbf4, the regulatory subunit for the cell-cycle kinase Cdc7 that initiates DNA replication. In Drosophila, the chiffon gene encodes two polypeptides with independent activities. Chiffon-A contains the conserved Dbf4 motifs and interacts with Cdc7 to form the Dbf4-dependent Kinase (DDK) complex, which is essential for a specialized form of DNA replication. In contrast, Chiffon-B binds the histone acetyltransferase Gcn5 to form the Chiffon histone acetyltransferase (CHAT) complex, which is necessary for histone H3 acetylation and viability. Previous studies have shown that the Chiffon-B region is only present within insects. However, it was unclear how widely the interaction between Chiffon-B and Gcn5 was conserved among insect species. To examine this, we performed yeast two-hybrid assays using Chiffon-B and Gcn5 from a variety of insect species and found that Chiffon-B and Gcn5 interact in Diptera species such as Australian sheep blowfly and yellow fever mosquito. Protein domain analysis identified that Chiffon-B has features of acidic transcriptional activators such as Gal4 or VP16. We propose that the CHAT complex plays a critical role in a biological process that is unique to Dipterans and could therefore be a potential target for pest control strategies.

Histone deacetylase 1 suppresses Krüppel homolog 1 gene expression and influences juvenile hormone action in Tribolium castaneum.

Posttranslational modifications, including acetylation and deacetylation of histones and other proteins, modulate hormone action. In Tribolium castaneum TcA cells, Trichostatin A, a histone deacetylase (HDAC) inhibitor, mimics juvenile hormone (JH) in inducing JH response genes (e.g., Kr-h1), suggesting that HDACs may be involved in JH action. To test this hypothesis, we identified genes coding for HDACs in T. castaneum and studied their function. Knockdown of 12 HDAC genes showed variable phenotypes; the most severe phenotype was detected in insects injected with double-stranded RNA targeting HDAC1 (dsHDAC1). The dsHDAC1-injected insects showed arrested growth and development and eventually died. Application of JH analogs hydroprene to T. castaneum larvae and JH III to TcA cells suppressed HDAC1 expression. Sequencing of RNA isolated from control and dsHDAC1-injected larvae identified 1,720 differentially expressed genes, of which 1,664 were up-regulated in dsHDAC1-treated insects. The acetylation levels of core histones were increased in TcA cells exposed to dsHDAC1 or JH III. ChIP assays performed using histone H2BK5ac antibodies showed an increase in acetylation in the Kr-h1 promoter region of cells exposed to JH III or dsHDAC1. Overexpression or knockdown of HDAC1, SIN3, or both resulted in a decrease or increase in Kr-h1 mRNA levels and its promoter activity, respectively. Overexpression of the JH receptor Methoprene tolerant (Met) was unable to induce Kr-h1 in the presence of HDAC1 or SIN3. These data suggest that epigenetic modifications influence JH action by modulating acetylation levels of histones and by affecting the recruitment of proteins involved in the regulation of JH response genes.

Histone deacetylase 3 is required for development and metamorphosis in the red flour beetle, Tribolium castaneum.

BACKGROUND: Hormones are chemical communication signaling molecules released into the body fluids to stimulate target cells of multicellular organisms. We recently showed that histone deacetylase 1 (HDAC1) plays an important role in juvenile hormone (JH) suppression of metamorphosis in the red flour beetle, Tribolium castaneum. Here, we investigated the function of another class I HDAC member, HDAC3, and show that it is required for the normal development of T. castaneum. RESULTS: RNA interference-mediated knockdown of the HDAC3 gene affected development resulting in abnormally folded wings in pupae and adults. JH analog, hydroprene, suppressed the expression of HDAC3 in T. castaneum larvae. The knockdown of HDAC3 during the final instar larval stage resulted in an increase in the expression of genes coding for proteins involved in JH action. Sequencing of RNA isolated from larvae injected with dsRNA targeting malE (E. coli gene, control) or HDAC3 followed by differential gene expression analysis identified 148 and 741 differentially expressed genes based on the P-value < 0.01 and four-fold difference, and the P-value < 0.05 and two-fold difference, respectively. Several genes, including those coding for myosin-I heavy chain (Myosin 22), Shaven, and nuclear receptor corepressor 1 were identified as differentially expressed genes in HDAC3 knockdown larvae. An increase in histone H3 acetylation, specifically H3K9, H3K18, and H3K27, was detected in HDAC3 knockdown insects. CONCLUSION: Overall, these data suggest that HDAC3 affects the acetylation levels of histones and influences the expression of genes coding for proteins involved in the regulation of growth, development, and metamorphosis.

Evaluation of inhibitor of apoptosis genes as targets for RNAi-mediated control of insect pests.

Apoptosis has been widely studied from mammals to insects. Inhibitor of apoptosis (IAP) protein is a negative regulator of apoptosis. Recent studies suggest that iap genes could be excellent targets for RNA interference (RNAi)-mediated control of insect pests. However, not much is known about iap genes in one of the well-known insect model species, Tribolium castaneum. The orthologues of five iap genes were identified in T. castaneum by searching its genome at NCBI (https://www.ncbi.nlm.nih.gov/) and UniProt (https://www.uniprot.org/) databases using Drosophila melanogaster and Aedes aegypti IAP protein sequences as queries. RNAi assays were performed in T. castaneum cell line (TcA) and larvae. The knockdown of iap1 gene induced a distinct apoptotic phenotype in TcA cells and induced 91% mortality in T. castaneum larvae. Whereas, knockdown of iap5 resulted in a decrease in cell proliferation in TcA cells and developmental defects in T. castaneum larvae which led to 100% mortality. Knockdown of the other three iap genes identified did not cause a significant effect on cells or insects. These data increase our understanding of iap genes in insects and provide opportunities for developing iap1 and iap5 as targets for RNAi-based insect pest control.

Correction to: Multiple functions of CREB-binding protein during postembryonic development: identification of target genes.

Following the publication of this article [1], the authors found that the primers listed for CREB-binding protein were not correct. This mistake occurred during assembly of the primer table and the authors apologize for this error. This correction does not change the data included in the paper, their interpretation nor the conclusions drawn.

Multiple functions of CREB-binding protein during postembryonic development: identification of target genes.

BACKGROUND: Juvenile hormones (JH) and ecdysteroids control postembryonic development in insects. They serve as valuable targets for pest management. Hence, understanding the molecular mechanisms of their action is of crucial importance. CREB-binding protein (CBP) is a universal transcriptional co-regulator. It controls the expression of several genes including those from hormone signaling pathways through co-activation of many transcription factors. However, the role of CBP during postembryonic development in insects is not well understood. Therefore, we have studied the role of CBP in postembryonic development in Tribolium, a model coleopteran insect. RESULTS: CBP is ubiquitously expressed in the red flour beetle, Tribolium castaneum. RNA interference (RNAi) mediated knockdown of CBP resulted in a decrease in JH induction of Kr-h1 gene expression in Tribolium larvae and led to a block in their development. Moreover, the injection of CBP double-stranded RNA (dsRNA) showed lethal phenotypes within 8 days of injection. RNA-seq and subsequent differential gene expression analysis identified CBP target genes in Tribolium. Knockdown of CBP caused a decrease in the expression of 1306 genes coding for transcription factors and other proteins associated with growth and development. Depletion of CBP impaired the expression of several JH response genes (e.g., Kr-h1, Hairy, early trypsin) and ecdysone response genes (EcR, E74, E75, and broad complex). Further, GO enrichment analyses of the downregulated genes showed enrichment in different functions including developmental processes, pigmentation, anatomical structure development, regulation of biological and cellular processes, etc. CONCLUSION: These data suggest diverse but crucial roles for CBP during postembryonic development in the coleopteran model insect, Tribolium. It can serve as a target for RNAi mediated pest management of this stored product pest.

Choosing the right interface for positive airway pressure therapy in patients with obstructive sleep apnea.

PURPOSE: Positive airway pressure (PAP) is the standard and most effective treatment for obstructive sleep apnea (OSA). It provides a continuous stream of air under positive pressure through the nose, mouth, or both, which prevents collapse of the upper airway. This allows the patient to breathe freely during sleep. The success of PAP therapy depends largely on the selection of the proper interface (mask). The choice and application of the interface in patients with OSA is a great challenge that greatly affects the long-term compliance to PAP therapy. METHODS: This article discusses the different types of masks that can be used in patients with OSA, including the differences between nasal, oro-nasal, and total face masks, breathing during wakefulness and sleep, and the impact of interface type on upper airway patency and mask fitting. We also discuss the steps to be considered in choosing the proper interface and potential problems that may arise during long-term use. RESULTS AND CONCLUSION: Current evidence suggests that the nasal mask is better tolerated, requires lower pressure to eliminate obstructive respiratory events, and is associated with a better sleep quality and better PAP therapy compliance. Nevertheless, the best mask is the one that patient will wear.

Do they hear what we speak? Assessing the effectiveness of communication to families of critically ill neurosurgical patients.

BACKGROUND AND AIMS: Clinician-family communication must be effective for medical decision making in any Intensive Care Unit (ICU) setting. We performed a prospective study to assess the effectiveness of communication to families of critically ill neurosurgical patients based on the two criteria of comprehension and satisfaction. MATERIALS AND METHODS: The study was conducted on 75 patients in a 15 bedded neurosurgical ICU. An independent investigator assessed the comprehension and satisfaction of families between the 3(rd) and the 5(th) day of admission in ICU. Comprehension was tested using three components, that is, comprehension of diagnosis, prognosis and treatment. The satisfaction was measured using a modified version of the Critical Care Family Needs Inventory (CCFNI) (score of 56-extreme dissatisfaction and 14-extreme satisfaction). RESULTS: Poor comprehension was noted in 52 representatives (71.2%). The mean satisfaction score as measured by the CCFNI score was 28. Factors associated with poor comprehension included increasing age of patient representative (P = 0.024), higher simplified acute physiology score (P = 0.26), nonoperated patients (P = 0.0087) and clinician estimation of poor prognosis (P = 0.01). Operated patients had significantly better satisfaction score (P = 0.04). CONCLUSION: Families of patients were reasonably satisfied, but had poor comprehension levels of the patient's illness. The severity of the patient's illness, poor prognosis as estimated by the physician and nonoperated patients were independent predictors of poor comprehension. Extra effort to communicate with patient representatives at risk of poor comprehension and provision of a family information leaflet could possibly remedy this situation.

N(alpha)-acetyltransferase 40-mediated histone acetylation plays an important role in ecdysone regulation of metamorphosis in the red flour beetle, Tribolium castaneum.

Histone acetylation, a crucial epigenetic modification, is governed by histone acetyltransferases (HATs), that regulate many biological processes. Functions of HATs in insects are not well understood. We identified 27 HATs and determined their functions using RNA interference (RNAi) in the model insect, Tribolium castaneum. Among HATs studied, N-alpha-acetyltransferase 40 (NAA40) knockdown caused a severe phenotype of arrested larval development. The steroid hormone, ecdysone induced NAA40 expression through its receptor, EcR (ecdysone receptor). Interestingly, ecdysone-induced NAA40 regulates EcR expression. NAA40 acetylates histone H4 protein, associated with the promoters of ecdysone response genes: EcR, E74, E75, and HR3, and causes an increase in their expression. In the absence of ecdysone and NAA40, histone H4 methylation by arginine methyltransferase 1 (ART1) suppressed the above genes. However, elevated ecdysone levels at the end of the larval period induced NAA40, promoting histone H4 acetylation and increasing the expression of ecdysone response genes. NAA40 is also required for EcR, and steroid-receptor co-activator (SRC) mediated induction of E74, E75, and HR3. These findings highlight the key role of ecdysone-induced NAA40-mediated histone acetylation in the regulation of metamorphosis.

Comparison of the effect of lignocaine instilled through the endotracheal tube and intravenous lignocaine on the extubation response in patients undergoing craniotomy with skull pins: A randomized double blind clinical trial.

BACKGROUND: A desirable combination of smooth extubation and an awake patient after neurosurgical procedures is difficult to achieve in patients with skull pins. Lignocaine instilled into endotracheal tube has been reported to suppress cough by a local mucosal anesthetizing effect. We aimed to evaluate if this effect will last till extubation, if given before pin removal. MATERIALS AND METHODS: A total of 114 patients undergoing elective craniotomy were divided into three groups and were given 1 mg/kg of intravenous (IV), 2% lignocaine (Group 1), placebo (Group 2) and 1 mg/kg of 2% lignocaine sprayed down the endotracheal tube (Group 3) before skull pin removal. The effectiveness of each to blunt extubation response was compared. Plasma levels of lignocaine were measured 10 min after administration of the study drug and at extubation. Sedation scores were noted, immediately after extubation and 10 min later. RESULTS: Two percent of lignocaine instilled through endotracheal route was not superior to the IV route or placebo in attenuating cough or hemodynamic response at extubation when given 20-30 min before extubation. The plasma levels of lignocaine (0.8 µg/ml) were not high enough even at the end of 10 min to have a suppressive effect on cough if given IV or intratracheally (IT). Lignocaine did not delay awakening in these groups. CONCLUSION: IT lignocaine in the dose of 1 mg/kg does not prevent cough at extubation if given 20-30 min before extubation. If the action is by a local mucosal anesthetizing effect, it does not last for 20-30 min to cover the period from pin removal to extubation.

Epigenomic reprogramming in iAs-mediated carcinogenesis.

Arsenic is a naturally occurring metal carcinogen found in the Earth's crust. Millions of people worldwide are chronically exposed to arsenic through drinking water and food. Exposure to inorganic arsenic has been implicated in many diseases ranging from acute toxicities to malignant transformations. Despite the well-known deleterious health effects of arsenic exposure, the molecular mechanisms in arsenic-mediated carcinogenesis are not fully understood. Since arsenic is non-mutagenic, the mechanism by which arsenic causes carcinogenesis is via alterations in epigenetic-regulated gene expression. There are two possible ways by which arsenic may modify the epigenome-indirectly through an arsenic-induced generation of reactive oxygen species which then impacts chromatin remodelers, or directly through interaction and modulation of chromatin remodelers. Whether directly or indirectly, arsenic modulates epigenetic gene regulation and our understanding of the direct effect of this modulation on chromatin structure is limited. In this chapter we will discuss the various ways by which inorganic arsenic affects the epigenome with consequences in health and disease.

Evaluation of the accuracy of manual and automatic scoring of a single airflow channel in patients with a high probability of obstructive sleep apnea.

BACKGROUND: ApneaLink (AL) is a single-channel type-4 device that measures airflow. A limited number of studies have assessed AL's usefulness in diagnosing obstructive sleep apnea (OSA) using automated scoring alone. This study was conducted to assess the sensitivity and specificity of AL in a selected group of people with clinical suspicion of OSA, using both automatic and manual scoring and comparing the results with those obtained for polysomnography (PSG). MATERIAL/METHODS: Simultaneous overnight recordings of in-laboratory PSG and AL were performed for 95 patients (mean age 46.3 ± 12.6 yr) with a high clinical suspicion of OSA. PSG was scored manually according to the American Academy of Sleep Medicine (AASM) guidelines. AL data were analyzed automatically using a manufacturer-provided computerized algorithm. Manual scoring of the AL flow signal followed the AASM guidelines for reduction in flow. RESULTS: The mean apnea hypopneas index (AHI) for PSG was 34.1 ± 32.4/hr. The AL Auto-AHI was 20.1 ± 25.2/h, and the AL Manual-AHI was 39.5 ± 30.4/h. The Pearson correlation coefficients were r=0.883 between PSG-AHI and AL Auto-AHI, and r=0.966 between PSG-AHI and AL Manual-AHI. At AHIs of 5, 10, 15, and 30, the AL Auto sensitivity/specificity was 0.79/0.68, 0.70/0.89, 0.64/0.94 and 0.63/0.98, and the AL Manual sensitivity/specificity was 1.00/0.43, 1.00/0.56, 0.98/0.58 and 1.00/0.80. CONCLUSIONS: Combining auto and manual scoring of data (automatic scoring followed by manual scoring) recorded by single-channel ApneaLink provides good diagnostic agreement with conventional PSG recordings.

Simulation with a colour indicator to help reduce contamination during airway management in COVID-19 times: An experience from a tertiary centre in India.

BACKGROUND AND AIMS: The coronavirus disease 2019 (COVID-19) pandemic has initiated modified protocols for aerosol-generating procedures. A simulation study using dye was conducted to highlight contamination at intubation and extubation and to encourage adherence to the new COVID-19 protocol among anaesthesia personnel in our institution. METHODS: A video demonstrating the new COVID-19 protocols was circulated in the Department of Anaesthesiology a week prior to the study. Thirty teams, each comprising an anaesthesia resident and a staff technician, were enroled. Each team was asked to demonstrate the steps of preparation, intubation and extubation on a mannequin in a COVID-19 scenario. Checklists were used to assess points of contamination and adherence to the protocols. Following debriefing, a repeat simulation was conducted. The use of a dye highlighted the points of contamination. The study subjects provided feedback on the usefulness of the session and practical difficulties encountered in adapting to the new protocols. RESULTS: The average contamination scores decreased by 3.4 (95% confidence interval (CI): 2.4-4.4, P < 0.001) in the post-debrief session. Adherence to the steps of the modified protocol improved by a score of 2.7 (CI: 3.6-1.83) among anaesthesiologists and by 4.3 (CI: 5.3-3.3) among technicians. Further, 93% felt that the use of the colour indicator reinforced awareness of the possible points of contamination. CONCLUSION: Simulation with a low-fidelity mannequin by using colour indicator for secretions is an effective teaching tool to reduce health hazards during airway management in COVID-19 times.

Histone Deacetylase 11 Knockdown Blocks Larval Development and Metamorphosis in the Red Flour Beetle, Tribolium castaneum.

Post-translational modifications (PTM) such as methylation, acetylation, phosphorylation, and ubiquitination of histones and other proteins regulate expression of genes. The acetylation levels of these proteins are determined by the balance of expression of histone acetyltransferase (HATs) and histone deacetylases (HDACs). We recently reported that class I HDACs (HDAC1 and HDAC3) play important roles in juvenile hormone (JH) suppression of metamorphosis in the red flour beetle, Tribolium castaneum. Here, we report on the function of a single class IV HDAC member, HDAC11. Injection of dsRNA targeting T. castaneum HDAC11 gene into newly molted last instar larvae induced knockdown of the target gene and arrested larval development and prevented metamorphosis into the pupal stage. Dark melanized areas were detected in larvae that showed developmental arrest and mortality. Developmental expression studies showed an increase in HDAC11 mRNA levels beginning at the end of the penultimate larval stage. These higher levels were maintained during the final instar larval and pupal stages. A JH analog, hydroprene, suppressed HDAC11 expression in the larvae. Sequencing of RNA isolated from control and dsHDAC11 injected larvae identified several differentially expressed genes, including those involved in JH action, ecdysone response, and melanization. The acetylation levels of core histones showed an increase in TcA cells exposed to dsHDAC11. Also, an increase in histone H3 acetylation, specifically H3K9, H3K18 and H3K27, were detected in HDAC11 knockdown larvae. These studies report the function of HDAC11 in insects other than Drosophila for the first time and show that HDAC11 influences the acetylation levels of histones and expression of multiple genes involved in T. castaneum larval development.

Efficacy of a multimodal intervention strategy in improving hand hygiene compliance in a tertiary level intensive care unit.

CONTEXT: The role of hand hygiene in preventing health care associated infections (HCAIs) has been clearly established. However, compliance rates remain poor among health care personnel. AIMS: a) To investigate the health care workers' hand hygiene compliance rates in the intensive care unit (ICU), b) to assess reasons for non-compliance and c) to study the efficacy of a multimodal intervention strategy at improving compliance. SETTINGS: A mixed medical-surgical ICU of a tertiary level hospital. DESIGN: A before-after prospective, observational, intervention study. MATERIALS AND METHODS: All health care personnel who came in contact with patients in the ICU were observed for their hand hygiene compliance before and after a multimodal intervention strategy (education, posters, verbal reminders and easy availability of products). A self-report questionnaire was also circulated to assess perceptions regarding compliance. Statistical analysis was done using χ(2) test or Fisher exact test (Epi info software). RESULTS: Hand hygiene compliance among medical personnel working in the ICU was 26% and the most common reason cited for non-compliance was lack of time (37%). The overall compliance improved significantly following the intervention to 57.36% (P<0.000). All health care worker groups showed significant improvements: staff nurses (21.48-61.59%, P<0.0000), nursing students (9.86-33.33%, P<0.0000), resident trainees (21.62-60.71%, P<0.0000), visiting consultants (22-57.14%, P=0.0001), physiotherapists (70-75.95%, P=0.413) and paramedical staff (10.71-55.45%, P< 0.0000). CONCLUSIONS: Hand hygiene compliance among health care workers in the ICU is poor; however, intervention strategies, such as the one used, can be useful in improving the compliance rates significantly.

Long-term follow-up of patients with narcolepsy-cataplexy treated with sodium oxybate (Xyrem).

OBJECTIVES: The clinical experience with sodium oxybate (Xyrem) in patients with narcolepsy-cataplexy is still limited, especially in children, elderly patients, and patients with concomitant obstructive sleep apnea (OSA). In this report, we describe 4 patients with narcolepsy and refractory cataplexy who were started on sodium oxybate and followed up for approximately 2 years, including an 11-year-old child and an elderly man with severe OSA. METHODS: The sodium oxybate dose was built up gradually until symptoms were controlled, adverse effects appeared, or the maximum nightly dose of 9.0 g was reached. On average, each subject underwent 4 sleep studies during follow-up after starting sodium oxybate. The nightly dose needed to control symptoms ranged from 5.0 to 9.0 g. RESULTS: Cataplexy, sleep paralysis, and sleep-onset hallucinations disappeared in all cases. In addition, daytime sleepiness decreased subjectively according to the Epworth Sleepiness Scale and objectively according to the Multiple Sleep Latency Test. Polysomnography demonstrated clear reductions in sleep latency, arousal index, and stage 1 sleep (N1). Slow-wave sleep (N3) and sleep efficiency increased with sodium oxybate treatment. Interestingly, the 11-year-old child and the elderly man with documented severe OSA on continuous positive airway pressure therapy demonstrated tolerability to sodium oxybate. Adverse effects included nausea, snoring, paresthesia, convulsion, and enuresis. However, all adverse effects disappeared after reduction of the dose. The beneficial effect of sodium oxybate persisted during the follow-up period. CONCLUSION: Sodium oxybate is an effective and well-tolerated medication for patients with refractory cataplexy. However, it requires special monitoring and follow-up by a specialized center. The improvement in clinical symptoms and sleep architecture seems to persist over time.

Metastatic phalangeal osteolysis as an initial presentation of carcinoma colon.

Metastatic malignancies of the hand are rare and usually develop from lung, breast, or kidney tumors. Metastases from tumors and sarcomas of the gastrointestinal system are even more uncommon. The authors report a case of differentiated adenocarcinoma of the colon in a 76-year-old man who presented with distal phalangeal metastasis and osteolysis in the form of a painful swelling at the tip of the right little finger of 6 months duration. Computed tomography of the abdomen and colonoscopy revealed a mass in the transverse colon. Diagnosis was confirmed by biopsy. Treatment was given with palliative local radiation and systemic chemotherapy. After 4 weeks of chemotherapy, the patient discontinued treatment and eventually succumbed to the disease.