Left ventricular free-wall rupture: An unusual presentation of non-bacterial thrombotic endocarditis.

Non-bacterial thrombotic endocarditis (NBTE) is a rare, often asymptomatic, condition. A 55-year-old woman presented with hemiparesis, facial palsy and chest pain. After urgent investigation, she was referred as a case of type A aortic dissection complicated by tamponade, myocardial infarction and stroke. Review of her imaging identified haemopericardium but no dissection, and emergency surgery proceeded considering her unstable condition. She underwent an emergency repair of left-ventricular free-wall rupture and excision of an aortic valve vegetation. Postoperative investigations confirmed a diagnosis of NBTE in the setting of a plexiform neurofibroma, and she was discharged 9 weeks later with residual neurological symptoms. This case poses a previously unreported acute presentation of NBTE and highlights the complexities in its diagnosis and management.

Comparative craniometric measurements of two Canid species in Egypt: the Egyptian red fox and the Egyptian Baladi dog.

The Egyptian red fox (Vulpes vulpes aegyptiaca) and Egyptian Baladi dog (Canis familiaris) are two members of the Family Canidae that are widely distributed in Egypt. The skulls of different Canid species vary greatly in their size and shape; therefore, they can be used as a tool to study the evolution and evolutionary history of these animals. The craniometric measurements are crucial for species identification and determination of the specific sites for nerve blocks. The present study compared the craniometric measurements of the red fox and Baladi dog skulls by measuring 47 parameters on each skull and calculation of 8 indices. The red fox skull had significantly lower values of 41 craniometric measurements (approximately 87% of the measurements done), including skull length, width, and height, cranial length and width, palatal and mandibular length, and dental measurements. In contrast, the red fox had significantly higher values of only 3 measurements (approximately 6% of the measurements done) including the tympanic bulla measurement. While only three skull measurements did not differ significantly between the red fox and dog. Statistics revealed that domestic dog had significantly higher values of foramen magnum and palatine indices, and significantly lower value of nasal index than those of red fox. The present work reported variations in the gross and craniometric measurements of skull between the red fox and dog. The measured cranial parameters of both adult animals provide valuable information that can be used in ecological studies, comparative anatomy, and clinical veterinary sciences.

Analgesia and spread of erector spinae plane block in breast cancer surgeries: a randomized controlled trial.

BACKGROUND: To evaluate the analgesic efficacy and spread of variable volumes of local anesthetics (LA) in Erector spinae plane block (ESPB). METHODS: Sixty patients aged between 18 and 50 years with an ASA I-II and scheduled for breast cancer surgery were randomized to receive either ESPB with 20 ml 0.25% bupivacaine (Standard volume ESPB), or with 40 ml 0.125% bupivacaine (High volume ESPB), or no ESPB (GA only group). The primary outcome was pain intensity evaluated by the visual analogue scale (VAS), 12 hours after surgery. P-values < 0.05 were considered the cutoff point for statistical significance. The secondary outcomes were pain at rest and pain on movement evaluated by the VAS, craniocaudal injectate spread, to paravertebral (PV) and epidural spaces assessed by CT, clinical dermatomal spread, level of sedation or agitation, and patient satisfaction with anesthesia and analgesia. RESULTS: VAS at rest 12 h after surgery was less in both intervention groups compared to the control (1.75 ± 0.79 vs. 1.6 ± 0.88 vs. 3.4 ± 1.96, p = 0.001). The LA had extended further in the high volume group than the standard volume group (11.20 ± 3.07 vs. 9.15 ± 2.54 vertebral levels, p = 0.027). No difference of the spread to PV or epidural spaces between the 2 intervention groups. More dermatomes were covered in the high volume group (7.20 ± 2.12 vs. 5.75 ± 1.37 dermatomes, p = 0.014). Agitation was higher in the GA only group than both ESPB groups in the first 8 postoperative hours. Patients were more satisfied in both ESPB groups than the GA only group. CONCLUSIONS: Preoperative ESPB is an excellent analgesic modality and it can also attenuate both postoperative agitation and sedation. Doubling the injectate volume enhances the craniocaudal spreading and may be useful for surgeries requiring multiple dermatomes. However, larger volume has no effect on analgesic efficacy or patient satisfaction as there is no further spread to the PV, epidural spaces or spinal nerve rami. TRIAL REGISTRATION: NCT04796363 (12/3/2021).

Role of Hypothermia in Adult Cardiac Surgery Patients: A Systematic Review and Meta-analysis.

OBJECTIVE: To review studies that assessed systemic hypothermia as an organ protection strategy in adults undergoing cardiac surgery with cardiopulmonary bypass. DESIGN: A systematic review and meta-analysis. SETTING AND PARTICIPANTS: Randomized controlled trials, irrespective of blinding, language, publication status, and date of publication, were identified by searching the Cochrane Central register of Controlled Trials, MEDLINE, and Embase until November 2020. Risk of bias assessment was performed according to Cochrane methodology. Treatment effects were expressed as risk ratios and 95% confidence intervals. Heterogeneity was expressed as I2. INTERVENTIONS: Systemic hypothermia. MEASUREMENTS AND MAIN RESULTS: Forty-eight trials enrolling 6,690 patients were included in the analysis. Methodologic quality of the studies included was low, mostly due to insufficient allocation concealment or blinding. Random-effects meta-analysis did not resolve uncertainty as to the risks and benefits for hypothermia versus normothermia for key primary and secondary outcomes, including mortality (1.21, 0.94 to 1.56, I2 = 0%) and brain injury (0.87, 0.67 to 1.14, I2 = 0%). Sensitivity analyses restricted to trials at low risk of important bias demonstrated higher mortality with hypothermia (1.70, 1.05 to 2.75, I2 = 0%), with little or no treatment effect on brain injury (1.01, 0.69 to 1.49, I2 = 0%). There was no interaction between cardioplegia temperature and the effects of cardiopulmonary bypass temperature on outcomes. There was insufficient evidence to assess the effects of hypothermia in noncoronary artery bypass graft surgery. CONCLUSION: The existing evidence for an organ-protective effect of hypothermia in adult cardiac surgery is of low quality and inconsistent.

Trends of repeat revascularization choice in patients with prior coronary artery bypass surgery.

OBJECTIVE: To examine rates and predictors repeat revascularization strategies (percutaneous coronary intervention [PCI] and coronary artery bypass grafting [CABG]) in patients with prior CABG. METHODS: Using the National Inpatient Sample, patients with a history of CABG hospitalized for revascularization by PCI or CABG from January 2004 to September 2015 were included. Regression analyses were performed to examine predictors of receipt of either revascularization strategy as well as in-hospital outcomes. RESULTS: The rate of redo CABG doubled between 2004 (5.3%) and 2015 (10.3%). Patients who underwent redo CABG were more comorbid and experienced significantly worse major adverse cardiovascular and cerebrovascular events (odds ratio [OR]: 5.36 95% CI 5.11-5.61), mortality (OR 2.84 95% CI 2.60,-3.11), bleeding (OR 5.97 95% CI 5.44-6.55) and stroke (OR 2.15 95% CI 1.92-2.41), but there was no difference in cardiac complications between groups. Thoracic complications were high in patients undergoing redo CABG (8%), especially in females. Factors favoring receipt of redo CABG compared to PCI included male sex, age < 80 years, and absence of diabetes and renal failure. CONCLUSION: Reoperation in patients with prior CABG has doubled in the United States over a 12-year period. Patients undergoing redo CABG are more complex and associated with worse clinical outcomes than those receiving PCI.

Pharmacological interventions for the prevention of renal injury in surgical patients: a systematic literature review and meta-analysis.

BACKGROUND: The aim of this systematic review was to summarise the results of randomised controlled trials (RCTs) that have evaluated pharmacological interventions for renoprotection in people undergoing surgery. METHODS: Searches were conducted to update a previous review using the Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE to August 23, 2019. RCTs evaluating the use of pharmacological interventions for renal protection in the perioperative period were included. The co-primary outcome measures were 30-day mortality and acute kidney injury (AKI). Pooled effect estimates were expressed as risk ratios (RRs) (95% confidence intervals). RESULTS: We included 228 trials enrolling 56 047 patients. Twenty-three trials were considered to be at low risk of bias across all domains. Atrial natriuretic peptides (14 trials; n=2207) reduced 30-day mortality (RR: 0.63 [0.41, 0.97]) and AKI events (RR: 0.43 [0.33, 0.56]) without heterogeneity. These effects were consistent across cardiac surgery and vascular surgery subgroups, and in sensitivity analyses restricted to studies at low risk of bias. Inodilators (13 trials; n=2941) reduced mortality (RR: 0.71 [0.53, 0.94]) and AKI events (RR: 0.65 [0.50, 0.85]) in the primary analysis and in cardiac surgery cohorts. Vasopressors (4 trials; n=1047) reduced AKI (RR: 0.56 [0.36, 0.86]). Nitric oxide donors, alpha-2-agonists, and calcium channel blockers reduced AKI in primary analyses, but not after exclusion of studies at risk of bias. Overall, assessment of the certainty of the effect estimates was low. CONCLUSIONS: There are multiple effective pharmacological renoprotective interventions for people undergoing surgery.

Incidence and predictors of postoperative ischemic stroke after coronary artery bypass grafting.

BACKGROUND: Data on the incidence and outcomes of ischemic stroke in patients undergoing coronary artery bypass grafting (CABG) in the current era are limited. The goal of this study was to examine contemporary trends, predictors, and outcomes of ischemic stroke following CABG in a large nationally representative database over a 12-year-period. METHODS: The National Inpatient Sample was used to identify all adult (≥18 years) patients who underwent CABG between 2004 and 2015. The incidence and predictors of post-CABG ischemic stroke were assessed and in-hospital outcomes of patients with and without post-CABG stroke were compared. RESULTS: Out of 2 569 597 CABG operations, ischemic stroke occurred in 47 279 (1.8%) patients, with a rising incidence from 2004 (1.2%) to 2015 (2.3%) (P < .001). Patient risk profiles increased over time in both cohorts, with higher Charlson comorbidity scores observed amongst stroke patients. Stroke was independently associated with higher rates of in-hospital mortality (3-fold), longer lengths of hospital stay (~6 more days), and higher total hospitalisation cost (~$80 000 more). Age ≥60 years and female sex (OR 1.33, 95% CI 1.31-1.36) were the strongest predictors of stroke (both P < .001). Further, on-pump CABG was not an independent predictor of stroke (P = .784). CONCLUSION: In this nationally representative study we have shown that the rates of postoperative stroke complications following CABG have increased over time to commensurate with a parallel increase in overall baseline patient risks. Given the adverse impact of stroke on in-hospital morbidity and mortality after CABG, further studies are warranted to systematically delineate factors contributing to this striking trend.

Preoperative C-reactive protein as a predictor of postoperative acute kidney injury in patients undergoing coronary artery bypass grafting.

C-reactive protein is a well-known marker of inflammation and may be preoperatively elevated in the absence of infection in adult cardiac surgery patients, indicating a baseline inflammatory process. We conducted a literature search to assess the available evidence on whether there is an association between preoperative C-reactive protein and acute kidney injury after coronary artery bypass grafting. Included only were observational studies which investigated this association. We excluded abstracts, case reports, animal studies and articles in languages other than English. Altogether, 199 papers were retrieved from the search strategy reported, of which 6 studies were included in the final review. The study types, publication details, patient groups and key results are tabulated. A qualitative assessment of these papers was conducted. We conclude that there is some evidence to support the association between high preoperative C-reactive protein level and postoperative acute kidney injury and complications after coronary artery bypass grafting. Owing to variability in acute kidney injury definitions and C-reactive protein levels for different cohorts in the observational studies reviewed, it is unclear from current evidence what serum C-reactive protein cut-off level is significantly associated with postoperative acute kidney injury. Further evidence is needed to investigate whether raised preoperative C-reactive protein in the absence of an infective cause could have a role in risk prediction models for cardiac surgery-associated acute kidney injury.

Early aortic repair and decompressive hemicraniectomy in aortic dissection with ischaemic stroke.

The presence of stroke in patients with type A acute aortic dissection confers worse clinical outcomes and represents a therapeutic dilemma. While emergency surgical repair is the ideal management strategy, the risk of further cerebral insult is a cause of concern, especially in the elderly moribund patient, where delayed repair or a conservative approach may be considered. A 67-year-old female presented with chest pain and left-sided hemiparesis and was diagnosed with extensive type A acute aortic dissection and ischaemic stroke secondary to right common carotid artery stenosis. She underwent two major operations (emergency dissection repair and hemicraniectomy) and sustained several complications. Despite her eventful postoperative recovery, she was discharged after 6 weeks to a neurorehabilitation unit with a mild neurological deficit. Due to subsequent pulmonary complications, the patient died 5 weeks later. The present report appraises the current evidence on the management of patients with type A acute aortic dissection presenting with neurological sequelae.

Are patient expectations associated with treatment outcomes in individuals with chronic low back pain? A systematic review of randomised controlled trials.

AIM: The importance of patient expectations (PEs) on treatment outcomes is poorly understood in clinical practice. The aim of this review is to investigate the evidence behind association between pre-treatment PEs and treatment outcomes such as pain intensity (PI), level of function (LF) and health-related quality of life (HRQoL) among individuals with chronic low back pain (CLBP). METHODS: A systematic search was conducted for randomised controlled trials published between 1946 and May 2019 across major databases using the key MeSH terminologies. The association between PEs and PI, LF and HRQoL were extracted and categorised into positive, negative or no association for analysing the data. A descriptive synthesis was conducted and the association between PEs and PI, LF and HRQoL were reported. RESULTS: Among the total of seven trials, two trials demonstrated a positive association between PEs and PI in short (≤6 weeks) and long term (>6 months), while another two trials demonstrated no association at medium term (>6 weeks-≤6 months). About four trials demonstrated a positive significant association between PEs and LF, 2 at medium and 2 at long terms. The only available trial demonstrated no association between PEs and HRQoL at medium term. CONCLUSION: PEs is associated with PI at short and long terms. Also, evidence suggests association between PEs and LF at medium and long terms. Currently, there is no evidence of association between PEs and HRQoL. Further studies with valid tools to measure PE are warranted among individuals with CLBP.

Myristica fragrans Kernels Prevent Paracetamol-Induced Hepatotoxicity by Inducing Anti-Apoptotic Genes and Nrf2/HO-1 Pathway.

Paracetamol is responsible for acute liver failure in humans and experimental animals when taken at high doses and transformed into a reactive metabolite by the liver cytochrome P450. On the other hand, nutmeg is rich with many phytochemical ingredients that are known for their ability to inhibit cytochrome P450. Hence, the present experiment was aimed at studying the hepatoprotective effect of Myristica fragrans (nutmeg), kernel extract (MFKE) in respect to paracetamol (acetaminophen; N-acetyl-p-amino-phenol (APAP))-induced hepatotoxicity in rats, focusing on its antioxidant, anti-inflammatory, and anti-apoptotic activities. Liver toxicity was induced in rats by a single oral administration of APAP (2 g/kg). To evaluate the hepatoprotective effect of MFKE against this APAP-induced hepatotoxicity, rats were pre-treated with either oral administration of MFKE at 300 mg/kg daily for seven days or silymarin at 50 mg/kg as a standard hepatoprotective agent. APAP intoxication caused a drastic elevation in liver function markers (transaminases, alkaline phosphatase, and total bilirubin), oxidative stress indicators (lipid peroxidation and nitric oxide), inflammatory biomarkers (tumour necrosis factor-α, interleukin-1ß, inducible nitric oxide synthase, and nuclear factor ĸB) and the pro-apoptotic BCL2 Associated X (Bax) and caspases-3 genes. Furthermore, analyses of rat liver tissue revealed that APAP significantly depleted glutathione and inhibited the activities of antioxidant enzymes in addition to downregulating two key anti-apoptotic genes: Cellular FLICE (FADD-like IL-1ß-converting enzyme)-inhibitory protein (c-FLIP) and B-cell lymphoma 2 (Bcl-2). Pre-treatment with MFKE, however, attenuated APAP-induced liver toxicity by reversing all of these toxicity biomarkers. This hepatoprotective effect of MFKE was further confirmed by improvement in histopathological findings. Interestingly, the hepatoprotective effect of MFKE was comparable to that offered by the reference hepatoprotector, silymarin. In conclusion, our results revealed that MFKE had antioxidant, anti-inflammatory, and anti-apoptotic properties, and it is suggested that this hepatoprotective effect could be linked to its ability to promote the nuclear factor erythroid 2⁻related factor 2 (Nrf2)/antioxidant responsive element (ARE) pathway.

Whole-genome comparison of high and low virulent Staphylococcus aureus isolates inducing implant-associated bone infections.

Staphylococcus aureus can cause wide range of infections from simple soft skin infections to severe endocarditis, bacteremia, osteomyelitis and implant associated bone infections (IABI). The focus of the present investigation was to study virulence properties of S. aureus isolates from acute and chronic IABI by means of their in vivo lethality, in vitro osteoblasts invasion, biofilm formation and subsequently whole genome comparison between high and low virulent strains. Application of insect infection model Galleria mellonella revealed high, intermediate and low virulence phenotypes of these clinical isolates, which showed good correlation with osteoblast invasion and biofilm formation assays. Comparative genomics of selected high (EDCC 5458) and low (EDCC 5464) virulent strains enabled the identification of molecular factors responsible for the development of acute and chronic IABI. Accordingly, the low virulent strain EDCC 5464 harbored point mutations resulting in frame shift mutations in agrC (histidine kinase in agr system), graS (histidine kinase in graSR, a two component system) and efeB (peroxidase in efeOBU operon, an iron acquisition system) genes. Additionally, we found a mobile element (present 11 copies in EDCC 5464) inserted at the end of ß-hemolysin (hlb) and sarU genes, which are involved in the pathogenesis and regulation of virulence gene expression in coordination with quorum sensing system. All these results are in good support with the low virulence behavior of EDCC 5464. From the previous literature, it is well known that agr defective S. aureus clinical strains are isolated from the chronic infections. Similarly, low virulent EDCC 5464 was isolated from chronic implant-associated bone infections infection whereas EDCC 5458 was obtained from acute implant-associated bone infections. Laboratory based in vitro and in vivo results and insights from comparative genomic analysis could be correlated with the clinical conclusion of IABIs and allows evidence-based treatment strategies based on the pathogenesis of the strain to cure life devastating implant-associated infections.

TLR9 mediates S. aureus killing inside osteoblasts via induction of oxidative stress.

BACKGROUND: Staphylococcus aureus is the principle causative pathogen of osteomyelitis and implant-associated bone infections. It is able to invade and to proliferate inside osteoblasts thus avoiding antibiotic therapy and the host immune system. Therefore, development of alternative approaches to stimulate host innate immune responses could be beneficial in prophylaxis against S. aureus infection. TLR9 is the intracellular receptor which recognizes unmethylated bacterial CpG-DNA and activates immune cells. Synthetic CpG-motifs containing oligodeoxynucleotide (CpG-ODNs) mimics the stimulatory effect of bacterial DNA. RESULTS: Osteoblast-like SAOS-2 cells were pretreated with CpG-ODN type-A 2216, type-B 2006, or negative CpG-ODN 2243 (negative control) 4 h before infection with S. aureus isolate EDCC 5055 (=DSM 28763). Intracellular bacteria were streaked on BHI plates 4 h and 20 h after infection. ODN2216 as well as ODN2006 but not ODN2243 were able to significantly inhibit the intracellular bacterial growth because about 31 % as well as 43 % of intracellular S. aureus could survive the pretreatment of SAOS-2 cells with ODN2216 or ODN2006 respectively 4 h and 20 h post-infection. RT-PCR analysis of cDNAs from SAOS-2 cells showed that pretreatment with ODN2216 or ODN2006 stimulated the expression of TLR9. Pretreatment of SAOS-2 cells with ODN2216 or ODN2006 but not ODN2243 managed to induce reactive oxygen species (ROS) production inside osteoblasts as measured by flow cytometry analysis. Moreover, treating SAOS-2 cells with the antioxidant Diphenyleneiodonium (DPI) obviously reduced S. aureus killing ability of TLR9 agonists mediated by oxidative stress. CONCLUSIONS: In this work we demonstrated for the first time that CPG-ODNs have inhibitory effects on S. aureus survival inside SAOS-2 osteoblast-like cell line. This effect was attributed to stimulation of TLR9 and subsequent induction of oxidative stress. Pretreatment of infected SAOS-2 cells with ROS inhibitors resulted in the abolishment of the CPG-ODNs killing effects.

Camel Milk: Potential Utility as an Adjunctive Therapy to Peg-IFN/RBV in HCV-4 Infected Patients in Egypt.

The present prospective study aims to investigate the potential therapeutic effect and the underlying mechanisms of drinking camel milk for 60 days as an adjunctive therapy to the standard treatment PEG/RBV. Twenty-five hepatitis C virus (HCV)-infected Egyptian patients, with mild to moderate parenchymal affection to mild cirrhosis were enrolled in this study after proper history taking and clinical examination. Their biomarkers were evaluated before and after the addition of camel milk. The improving effect of camel milk was reflected on the marked inhibition of the serum levels of the proinflammatory markers, viz., tumor necrosis factor-α, monocyte chemotactic protein-1, hyaluronic acid, and TGF-ß1, besides PCR, AST, ALT, GGT, bilirubin, prothrombin time, INR, and alpha-fetoprotein. In addition, camel milk elevated significantly (P < 0.001) the serum levels of albumin, the antiapoptotic protein BCL-2, the total antioxidant capacity, interleukin-10, and vitamin D. In conclusion, our study revealed a regulatory function of camel milk on multiple parameters of inflammatory mediators, immunomodulators, antiapoptosis, and antioxidants, giving insight into the potential therapeutic benefit underlying the anti-HCV actions of camel milk. The limitations of the current study include the small sample size recruited and the failure to test it on cohorts with severe stages of hepatitis; like Child-Pugh stage C, and hepatocellular carcinoma.

An observational cohort study of patients with newly diagnosed digital ulcer disease secondary to systemic sclerosis registered in the EUSTAR database.

OBJECTIVES: This study describes clinical characteristics, prognostic factors, and quality of life in patients with newly diagnosed (incident) digital ulcers (DU). METHODS: Observational cohort study of 189 consecutive SSc patients with incident DU diagnosis identified from the EUSTAR database (22 centres in 10 countries). Data were collected from medical charts and during one prospective visit between 01/2004 and 09/2010. RESULTS: Median age at DU diagnosis was 51 years, majority of patients were female (88%), and limited cutaneous SSc was the most common subtype (61%). At incident DU diagnosis, 41% of patients had one DU and 59% had ≥2 DU; at the prospective visit 52% had DU. Pulmonary arterial hypertension (PAH) and multiple DU at diagnosis were associated with presence of any DU at the prospective visit (odds ratios: 4.34 and 1.32). During the observation period (median follow-up was 2 years) 127 patients had ≥1 hospitalisation. The event rate of new DU per person-year was 0.66, of DU-associated complications was 0.10, and of surgical or diagnostic procedures was 0.12. At the prospective visit, patients with ≥1 DU reported impairment in daily activities by 57%, those with 0 DU by 37%. The mean difference between patients with or without DU in the SF-36 physical component was 2.2, and in the mental component 1.4. DU patients were not routinely prescribed endothelin receptor antagonists or prostanoids. CONCLUSIONS: This real world cohort demonstrates that DU require hospital admission, and impair daily activity. PAH and multiple DU at diagnosis were associated with future occurrence of DU.

The intracellular sRNA transcriptome of Listeria monocytogenes during growth in macrophages.

Small non-coding RNAs (sRNAs) are widespread effectors of post-transcriptional gene regulation in bacteria. Currently extensive information exists on the sRNAs of Listeria monocytogenes expressed during growth in extracellular environments. We used deep sequencing of cDNAs obtained from fractioned RNA (<500 nt) isolated from extracellularly growing bacteria and from L. monocytogenes infected macrophages to catalog the sRNA repertoire during intracellular bacterial growth. Here, we report on the discovery of 150 putative regulatory RNAs of which 71 have not been previously described. A total of 29 regulatory RNAs, including small non-coding antisense RNAs, are specifically expressed intracellularly. We validated highly expressed sRNAs by northern blotting and demonstrated by the construction and characterization of isogenic mutants of rli31, rli33-1 and rli50* for intracellular expressed sRNA candidates, that their expression is required for efficient growth of bacteria in macrophages. All three mutants were attenuated when assessed for growth in mouse and insect models of infection. Comparative genomic analysis revealed the presence of lineage specific sRNA candidates and the absence of sRNA loci in genomes of naturally occurring infection-attenuated bacteria, with additional loss in non-pathogenic listerial genomes. Our analyses reveal extensive sRNA expression as an important feature of bacterial regulation during intracellular growth.

From Medical Analgesic to Recreational Use: A Rare Case of Acute Myelitis Caused by Laughing Gas Abuse.

Nitrous oxide, commonly known as laughing gas, which is originally intended to be used in various industries as well as for legitimate medical purposes, has unfortunately come to be used recreationally. However, it is crucial to recognize that the seemingly innocent recreational use of nitrous oxide can have serious repercussions on one's health. When consumed in excessive quantities and for prolonged periods, this substance can lead to serious adverse effects. In this article, we shed light on the abuse potential of the substance by discussing a distressing case of a young nitrous oxide user who developed severe myelitis.

Comparative genomics and transcriptomics of lineages I, II, and III strains of Listeria monocytogenes.

BACKGROUND: Listeria monocytogenes is a food-borne pathogen that causes infections with a high-mortality rate and has served as an invaluable model for intracellular parasitism. Here, we report complete genome sequences for two L. monocytogenes strains belonging to serotype 4a (L99) and 4b (CLIP80459), and transcriptomes of representative strains from lineages I, II, and III, thereby permitting in-depth comparison of genome- and transcriptome -based data from three lineages of L. monocytogenes. Lineage III, represented by the 4a L99 genome is known to contain strains less virulent for humans. RESULTS: The genome analysis of the weakly pathogenic L99 serotype 4a provides extensive evidence of virulence gene decay, including loss of several important surface proteins. The 4b CLIP80459 genome, unlike the previously sequenced 4b F2365 genome harbours an intact inlB invasion gene. These lineage I strains are characterized by the lack of prophage genes, as they share only a single prophage locus with other L. monocytogenes genomes 1/2a EGD-e and 4a L99. Comparative transcriptome analysis during intracellular growth uncovered adaptive expression level differences in lineages I, II and III of Listeria, notable amongst which was a strong intracellular induction of flagellar genes in strain 4a L99 compared to the other lineages. Furthermore, extensive differences between strains are manifest at levels of metabolic flux control and phosphorylated sugar uptake. Intriguingly, prophage gene expression was found to be a hallmark of intracellular gene expression. Deletion mutants in the single shared prophage locus of lineage II strain EGD-e 1/2a, the lma operon, revealed severe attenuation of virulence in a murine infection model. CONCLUSION: Comparative genomics and transcriptome analysis of L. monocytogenes strains from three lineages implicate prophage genes in intracellular adaptation and indicate that gene loss and decay may have led to the emergence of attenuated lineages.

A randomized, double-blind, prospective study of caspofungin vs. amphotericin B for the treatment of invasive candidiasis in newborn infants.

BACKGROUND: Caspofungin is an echinocandin agent with fungicidal activity against Candida species. OBJECTIVE: To assess the efficacy, safety and tolerability of caspofungin relative to amphotericin B in neonates with invasive candidiasis. PATIENTS AND METHODS: Thirty-two neonates with invasive candidiasis were randomly assigned to receive either caspofungin (n = 15) or amphotericin B (n = 17). Efficacy was evaluated, with a successful outcome defined as fulfilling all the components of a prespecified five-part composite endpoint. Evaluation of safety was done by monitoring drug-related adverse events. RESULTS: At the end of intravenous therapy, evaluation showed that caspofungin was superior, with a favorable response in 86.7% of patients as compared with 41.7% of those who received amphotericin B (p = 0.04). There were significantly fewer adverse events in the caspofungin group than in the amphotericin B group. CONCLUSION: Caspofungin is more effective, safer and alternative to amphotericin B for the treatment of invasive candidiasis in newborn infants.

Modulatory Effect of Papaya Extract against Chlorpyrifos-Induced Oxidative Stress, Immune Suppression, Endocrine Disruption, and DNA Damage in Female Clarias gariepinus.

Chlorpyrifos (CPF) is one of the widely used organophosphorus pesticides in agriculture activities and its presence in the aquatic environment has been broadly recorded. In the present study, we investigated the effect of CPF exposure on oxidative stress, innate immunity, sexual hormones, and DNA integrity of female African catfish, Clarias gariepinus, in addition to the potential use of dietary supplementation of papaya, Carica papaya (CP), extract against CPF toxicity. Apparent healthy female catfish (300 ± 10 g) were divided into four groups with three replicates each. The first group served as the negative control (fed on a basal diet) and the other groups exposed to CPF (8.75 µg/L) with or without CP extract (250 mg/kg body weight) for six weeks. The results revealed that CPF exposure exhibited marked elevations in stress markers (glucose and cortisol), serum aspartate aminotransferase, alanine aminotransferase activities, testosterone, and luteinizing hormone level. Moreover, CPF increased the percentage of hepatic DNA damage. In addition, catfish exposed to CPF experienced significant decline in serum total protein, albumin, follicles stimulating hormone, estradiol hormone levels, AChE, immunoglobulin, and lysozyme activity. CPF induced significantly oxidative stress in hepatic and renal tissues. The dietary supplementation with CP extract at a level of 250 mg/kg body weight succeeded to alleviate the negative effects of CPF on the physiological, immunological, and antioxidant status of female catfish. In addition, CP extract alleviated the endocrine disruption and hepatic DNA damage and counteracted the subchronic CPF toxicity in female African catfish. Finally, the CP extract may be used as a feed additive in the aquatic diet.