Systemic artery to pulmonary artery aneurysm malformations associated with variants at MCF2L.

Arteriovenous malformations (AVM) are characterized by abnormal vessels connecting arteries and veins resulting in a disruption of normal blood flow. Hereditary hemorrhagic telangiectasia (HHT) is the most common cause of pulmonary AVM characterized by a right to left shunt. Here we describe a distinct malformation where the flow of blood was from a systemic artery to the pulmonary artery (PA) resulting in a left to right shunt instead of the right to left shunt seen in individuals with HHT. This distinct malformation was identified in seven probands, one from a multiplex family containing 10 affected individuals from five generations. To identify the molecular basis of this distinct malformation, we performed exome sequencing (ES) on the seven probands and the affected paternal female cousin from the multiplex family. PhenoDB was used to prioritize candidate causative variants along with burden analysis. We describe the clinical and radiological details of the new systemic artery to PA malformation with or without pulmonary artery aneurysm (SA-PA(A)) and recommend distinct treatment techniques. Moreover, ES analysis revealed possible causative variants identified in three families with variants in a novel candidate disease gene, MCF2L. Further functional studies will be necessary to better understand the molecular mechanisms involved on SA-PA(A) malformation, however our findings suggest that MCF2L is a novel disease gene associated with SA-PA(A).

Isolation and Identification of Streptomyces spp. from Desert and Savanna Soils in Sudan.

The purpose of this study was to investigate streptomycete populations in desert and savanna ecozones in Sudan and to identify species based on 16S rRNA gene sequences. A total of 49 different Streptomyces phenotypes (22 from sites representing the desert and semi-desert ecozone; 27 representing the savanna ecozone) have been included in the study. The isolates were characterized phenotypically and confirmed using 16S rRNA gene sequence analysis. The two ecozones showed both similarities and uniqueness in the types of isolates. The shared species were in cluster 1 (Streptomyces (S.) werraensis), cluster 2 (Streptomyces sp.), cluster 3 (S. griseomycini-like), and cluster 7 (S. rochei). The desert ecozone revealed unique species in cluster 9 (Streptomyces sp.) and cluster 10 (S. griseomycini). Whereas, the savanna ecozone revealed unique species in cluster 4 (Streptomyces sp.), cluster 5 (S. albogriseolus/ S. griseoincarnatus), cluster 6 (S. djakartensis), and cluster 8 (Streptomyces sp.). Streptomycetes are widely distributed in both desert and the savanna ecozones and many of these require full descriptions. Extending knowledge on Streptomyces communities and their dynamics in different ecological zones and their potential antibiotic production is needed.

A multimodality approach to decreasing ICU infections by hydrogen peroxide, silver cations, and compartmentalization.

PURPOSE: Hospital-acquired infections in the Intensive Care Unit (ICU) account for an increase in morbidity and mortality leading to serious health complications. This study aims to determine the effect of a multimodality approach including disinfection and physical separation on the infections prevailing in ICU. METHODS: The study employed prospective cross-over analysis to assess the 738 individuals (560 males and 178 females) at the ICU, Aseer Central Hospital, Saudi Arabia. The intervention programs were carried out for 3 years (2013-2015). It included the application of hydrogen peroxide and silver cations, physical separation, and compartmentalization of ICU. Acinetobacter spp., E. coli, and staphylococci were isolated, identified, and used to evaluate the efficacy of the intervention program. RESULTS: The results provide endotracheal tube as the main specimen type (34.7%) followed by blood (29.1%), tracheal secretion (7.7%), wound (6%), urine (5.7%), throat swab (5.4%), sputum (3.7%), and other specimens (7.7%). It also showed the infection rate decreased from 14.3% to 4% in the last three months after continuous interventions (R2 = 0.44). There was a decrease in the occurrence of bacteria after an intervention (p = 0.036). CONCLUSION: The outcome of the study revealed that mist and separation measures offered a significant decrease in infections at the ICU as per the measurement of the most hazardous nosocomial pathogens.

Clinical Relevance and Antimicrobial Profiling of Methicillin-Resistant Staphylococcus aureus (MRSA) on Routine Antibiotics and Ethanol Extract of Mango Kernel (Mangifera indica L.).

Methicillin-resistant Staphylococcus aureus (MRSA) is known for serious health problems. Testing new inexpensive natural products such as mango kernel (Mangifera indica L., Anacardiaceae) may provide alternative and economically viable anti-MRSA drugs. In the current study, we screened clinical isolates from Aseer Central Hospital, Saudi Arabia, during 2012-2017 for MRSA and tested an ethanolic extract of mango kernel for anti-MRSA activity. Brief confirmation of MRSA was performed by the Vitek 2 system, while antibiotic sensitivity of strains was tested for their clinical relevance. The In vitro disc diffusion method was used to test the anti-MRSA activity of the ethanolic mango kernel extract. The antimicrobial activity of mango kernel was compared to that of standard drugs (oxacillin and vancomycin). Of the identified 132 S. aureus strains, 42 (31.8%) were found to be MRSA and their prevalence showed a clear increase during the last two years (2016-2017; p < 0.001). MRSA strains showed 100% sensitivity to vancomycin, teicoplanin, linezolid, tetracycline, daptomycin, tigecycline, and tobramycin and 100% resistance to ampicillin and 98% to penicillin. The ethanolic extracts of mango kernel were found active against both S. aureus and the MRSA strains. Inhibitory activities (mean ± SE) were achieved at concentrations of 50 mg/mL (20.77 ± 0.61), 5 mg/mL (16.18 ± 0.34), and 0.5 mg/mL (8.39 ± 0.33) exceeding that of vancomycin (p=0.0162). MRSA strains were sensitive to mango kernel extracts when compared to vancomycin. Therefore, ethanolic extracts of mango kernel can be escalated to animal model studies as a promising leading anti-MRSA drug candidate and can be an economic alternative to high-priced synthetic antibiotics.

Diversity and geographic distribution of soil streptomycetes with antagonistic potential against actinomycetoma-causing Streptomyces sudanensis in Sudan and South Sudan.

BACKGROUND: Production of antibiotics to inhibit competitors affects soil microbial community composition and contributes to disease suppression. In this work, we characterized whether Streptomyces bacteria, prolific antibiotics producers, inhibit a soil borne human pathogenic microorganism, Streptomyces sudanensis. S. sudanensis represents the major causal agent of actinomycetoma - a largely under-studied and dreadful subcutaneous disease of humans in the tropics and subtropics. The objective of this study was to evaluate the in vitro S. sudanensis inhibitory potential of soil streptomycetes isolated from different sites in Sudan, including areas with frequent (mycetoma belt) and rare actinomycetoma cases of illness. RESULTS: Using selective media, 173 Streptomyces isolates were recovered from 17 sites representing three ecoregions and different vegetation and ecological subdivisions in Sudan. In total, 115 strains of the 173 (66.5%) displayed antagonism against S. sudanensis with different levels of inhibition. Strains isolated from the South Saharan steppe and woodlands ecoregion (Northern Sudan) exhibited higher inhibitory potential than those strains isolated from the East Sudanian savanna ecoregion located in the south and southeastern Sudan, or the strains isolated from the Sahelian Acacia savanna ecoregion located in central and western Sudan. According to 16S rRNA gene sequence analysis, isolates were predominantly related to Streptomyces werraensis, S. enissocaesilis, S. griseostramineus and S. prasinosporus. Three clusters of isolates were related to strains that have previously been isolated from human and animal actinomycetoma cases: SD524 (Streptomyces sp. subclade 6), SD528 (Streptomyces griseostramineus) and SD552 (Streptomyces werraensis). CONCLUSION: The in vitro inhibitory potential against S. sudanensis was proven for more than half of the soil streptomycetes isolates in this study and this potential may contribute to suppressing the abundance and virulence of S. sudanensis. The streptomycetes isolated from the mycetoma free South Saharan steppe ecoregion show the highest average inhibitory potential. Further analyses suggest that mainly soil properties and rainfall modulate the structure and function of Streptomyces species, including their antagonistic activity against S. sudanensis.

Basidiobolus haptosporus-like fungus as a causal agent of gastrointestinal basidiobolomycosis.

Basidiobolus species were isolated from colonic biopsy samples of patients with gastrointestinal basidiobolomycosis (GIB) in southern Saudi Arabia. Isolated fungi were initially identified using classical mycological tools and confirmed by sequence analysis of the large subunit ribosomal RNA gene. Phenotypic tests revealed zygomycete-like fungi which conform to those of Basidiobolus species. Five sequenced strains formed a monophyletic clade in the 28S ribosomal RNA gene phylogenetic tree. They shared 99.97% similarity with B. haptosporus and 99.97% with B. haptosporus var. minor, and relatively lower similarity with B. ranarum (99.925%). The study suggests a new and a serious causal agent of GIB related to Basidiobolus haptosporus. These isolates are not related to B. ranarum, which is commonly linked to this disease.

Fungal peritonitis caused by Pichia kudriavzevii following sleeve gastrectomy.

A 23-year-old female, who had undergone a sleeve gastrectomy two weeks earlier, presented with abdominal complaints. A CT scan showed portal vein thrombosis, bowel ischemia, and intra-abdominal sepsis. Anastomosis and antibiotic therapy were not successful, and the patient went into multi-organ failure and died. Multiple cultures revealed a yeast fungus confirmed as Pichia kudriavzevii using rRNA gene sequencing. We report the first case of peritonitis in association with P kudriavzevii. In addition to the abdominal complications and surgical interventions, the yeast was found to have significantly contributed to the patient's death. SIMILAR CASES PUBLISHED: None. CONFLICT OF INTEREST: None.

Antimicrobial Efficiency of Essential Oils from Traditional Medicinal Plants of Asir Region, Saudi Arabia, over Drug Resistant Isolates.

Antimicrobial resistance (AMR) is a recurring global problem, which constantly demands new antimicrobial compounds to challenge the resistance. It is well known that essential oils (EOs) have been known for biological activities including antimicrobial properties. In this study, EOs from seven aromatic plants of Asir region of southwestern Saudi Arabia were tested for their antimicrobial efficacy against four drug resistant pathogenic bacterial isolates (Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli, and Streptococcus typhimurium) and one fungal isolate (Candida albicans). Chemical compositions of EOs were determined by gas chromatography-mass spectrometry (GC-MS). The results revealed that EOs from Mentha cervina, Ocimum basilicum, and Origanum vulgare proved most active against all isolates with inhibitory zone range between 17 and 45 mm. The lowest minimum inhibitory concentration (MIC) of 0.025mg/ml was observed for Staph. aureus and Streptococcus pyogenes with EO of Origanum vulgare. All the three EOs showed significant anticandida activity. The results related to EOs from Mentha cervina, Ocimum basilicum, and Origanum vulgare demonstrated significant antimicrobial efficacy against drug resistant microorganisms.

Fungal keratitis caused by a rare ocular pathogen, Gjaerumia minor: A case report.

Fungal keratitis is an important infection of the eye that may cause devastating effects. Keratitis caused by fungi has been described in many parts of the world mainly in tropical countries. The objective of this study is to report a serious eye infection in an adult with a known history of diabetes caused by an uncommon yeast fungus with details of clinical findings and laboratory investigations. Left eye visual acuity was no perception of light due to end stage neovascular glaucoma. The patient was pseudophakic in both eyes. Culture of a corneal scraping showed yeast like organism on Sabouraud dextrose agar. Gjaerumia minor, a rare yeast but with history of a pulmonary infection in the region, was confirmed with 98% similarity in the large subunit ribosomal RNA gene (accession KY690175). Topical Amphotericin B and oral fluconazole were initiated. The patient showed gradual improvement, epithelial defect healed, infiltration steadily regressed and hypopyon disappeared. We report the first case of fungal keratitis caused by G. minor in Saudi Arabia. Fungal Keratitis should be considered in cases where clinical response to the conventional antibacterial antibiotic treatment is not optimal.

Multidrug-Resistant Acinetobacter baumannii: An Emerging Health Threat in Aseer Region, Kingdom of Saudi Arabia.

OBJECTIVE: The study aims to determine the prevalence of multidrug-resistant A. baumannii in Aseer Region, Kingdom of Saudi Arabia. METHODS: This study evaluated the antibiotic susceptibility of ninety-four (n = 94) clinical isolates of A. baumannii. The isolates were collected from the south region of Saudi Arabia, and notably Aseer Region, during the period from 15 October 2014 to 15 January 2015. The isolates were tentatively identified as A. baumannii by routine bench tests and were confirmed by using VITEK® 2 Compact. The latest instrument was used to identify antibiotic susceptibility of these isolates. RESULTS: Antibiotic susceptibility in this study showed that 69% of these isolates were multidrug-resistant strains. Moreover, they were highly resistant to carbapenem drugs. Several strains of these isolates were found to be extremely resistant to test antibiotics and were only sensitive to one or two of them. CONCLUSION: High rate of multidrug-resistant A. baumannii bacteraemia has emerged in the south region of Saudi Arabia as an important health problem. Therefore, it is considered as a new threat in hospitals, which requires a tremendous effort to stop its escalation and spread.

Multidrug resistance Acinetobacter species at the intensive care unit, Aseer Central Hospital, Saudi Arabia: A one year analysis.

OBJECTIVE: To identify and to determine the antimicrobial susceptibility of Acinetobacter baumannii (A. baumannii) clinical isolates from ICU at Aseer Central Hospital. METHODS: The study was conducted in the Intensive Care Unit, Aseer Central Hospital, Saudi Arabia over 13 months period (2014-2015). Acinetobacter species (n = 105) were isolated from various clinical samples. Isolates were identified using selected phenotypic criteria and confirmed using the Vitek 2 automated system. This system was used to determine the susceptibilities of 21 antimicrobial agents. Patients, isolates and drug data were analyzed using the SPSS statistical software package to determine some epidemiological and microbiological patterns. RESULTS: Of the 105 stains, A. baumannii accounted for 49 (46.67%), A. baumannii complex, 19 (18.09%), A. baumannii/haemolyticus 32 (30.47), Acinetobacter haemolyticus 4 (3.81%), Acinetobater lwoffii 1 (0.95%) and unidentified Acinetobater species 2 (1.3%). Of the 105 Acinetobacter strains, 103 (98.1%) were found multidrug resistant (MDR). A. baumannii strain were 100% sensitive to colistin and 74.5% to trimethoprim + sulfamethoxazole. The remaining 19 antimicrobial agents revealed low or no sensitivities: amikacin 16.3%; ampicillin 7.7%; ceftazidime, 7.3%. Distribution of similar sensitivities was shown by other Acinetobacter species. Mean number of isolates from males and females indicates no statistical variation (P = 0.867) whereas age groups showed significant differences (P = 0.008) as it is clear from the high percentage of infected individuals more than 60 years followed by those aged 20-29 years old (19.05%). Upper respiratory tract (30.48%), lower respiratory tract (47.65%) and subcutaneous tissue (9.5%) were the main sources of Acinetobacter spp. but mean numbers of isolates from these specimens indicate no discrepancy between specimens (P = 0.731). CONCLUSIONS: Acinetobacter species including A. baumannii were found MDR (98.1%) according to the current Acinetobacter spp. antimicrobial categorization. Approximately half of these strains were A. baumannii. All Acinetobacter species were 100% sensitive to colistin and to some extent to trimethoprim + sulfamethoxazole (74.5%). ICU-acquired pneumonia among patients over 60 years of age who spend prolong times at artificial ventilations made up the majority of the cases.

Aggressive cutaneous zygomycosis caused by Apophysomyces variabilis in an immunocompetent child.

A zygomycetous fungus was observed in a biopsy of a 9-year-old male. The patient was presented with severe cutaneous lesions subsequent to a traumatic car accident. Following fungal detection, antifungal treatment was prescribed but condition deteriorated rapidly and above knee amputation was done as lifesaving and to control fungal infection. Analysis of the 28 S rRNA gene (accession KT149770) aligned the isolate with members of the genus Apophysomyces and the pathogen was identified as Apophysomces variabilis.

Transcatheter and endovascular stent graft management of coarctation-related pseudoaneurysms.

OBJECTIVE: Surgical correction of congenital aortic coarctation can lead to a number of important problems including late pseudoaneurysm formation. Redo surgery has a significant risk. Endovascular stent graft repair is increasingly used but there are limited data regarding this indication. We describe the experience of two UK congenital referral centres. DESIGN: Retrospective analysis of patients treated with endovascular aortic stent grafting for late pseudoaneurysms. SETTING: Two UK congenital heart centres, Bristol Heart Institute and Leeds General Infirmary. PATIENTS: 17 patients were treated 2006-2012. This represents all patients treated with this technique. MAIN OUTCOME MEASURES: Procedural and postprocedure success and complications. RESULTS: The average time from index repair to endovascular repair of pseudoaneurysm was 24.6 years. The majority (70.6%) had patch aortoplasty as the original surgical procedure and 41.2% were not under follow-up or discharged. Stent grafting procedural success rate was 100%. Median hospital stay postprocedure was 3 days. There was no procedural mortality or immediate complication. There were four minor early and three minor late complications. Imaging follow-up was available for an average of 31.6 months (range 6-65 months). All patients have demonstrated positive remodelling of the pseudoaneurysm with no incidence of continued expansion or stent graft failure up to 5 years following implant. CONCLUSIONS: Endovascular stent graft treatment of pseudoaneurysms show promising results in a population who have a high risk of surgical re-intervention. Complication rates appear to be low and recovery is quick. Longer-term data remain essential to scrutinise stent graft performance in this situation.

Binding affinities and activation of Asp712Ala and Cys100Ser mutated kinin B1 receptor forms suggest a bimodal scheme for the molecule of bound-DABK.

Mutant forms of kinin B(1) receptor (B(1)R) and analogs of the full agonist des-Arg(9)-bradykinin (DABK) were investigated aiming to verify the importance of selected receptor residues and of each agonist-peptide residue in the specific binding and activation. Linked by a specific disulfide bond (Cys(100)-Cys(650)), the N-terminal (N(t)) and the EC3 loop C-terminal (C(t)) segments of angiotensin II (AngII) receptor 1 (AT(1)R) have been identified to form an extracellular site for binding the agonist N(t) segment (Asp(1) and Arg(2) residues). Asp(712) residue at the receptor EC3 loop binds the peptide Arg(2) residue. By homology, a similar site might be considered for DABK binding to B(1)R since this receptor contains the same structural elements for composing the site in AT(1)R, namely the disulfide bond and the EC3 loop Asp(712) residue. DABK, Ala(n)-DABK analogs (n=Ala(1)-, Ala(2)-, Ala(3)-, Ala(4)-, Ala(5)-, Ala(6)-, Ala(7)-, Ala(8)-DABK), and other analogs were selected to binding wild-type, Asp712Ala and Cys100Ser mutated B(1)R receptors. The results obtained suggested that the same bimodal scheme adopted for AngII-AT(1)R system may be applied to DABK binding to B(1)R. The most crucial similarity in the two cases is that the N(t) segments of peptides equally bind to the homologous Asp(712) residue of both AT(1)R and B(1)R extracellular sites. Confirming this preliminary supposition, mutation of residues located at the B(1)R extracellular site as EC3 loop Asp(712) and Cys(100) caused the same modifications in biological assays observed in AT(1)R submitted to homologous mutations, such as significant weakening of agonist binding and reduction of post-receptor-activation processes. These findings provided enough support for defining a site that determines the specific binding of DABK to B(1)R receptors.

Efficacy of percutaneous closure of patent foramen ovale: comparison among three commonly used occluders.

BACKGROUND: Percutaneous closure of patent foramen ovale (PFO) is standard treatment for patients with paradoxical embolism but studies examining the efficacy of the various occluders are lacking. OBJECTIVE: To evaluate short- and medium-term closure rates of three common occluders. METHODS: One hundred and sixty-six adults (47±12 (18-81 years)) were evaluated with transthoracic bubble echocardiography before and after PFO closure. Only patients with large PFOs were included (>30 bubbles in the left heart after Valsalva). RESULTS: Three occluders were used: Amplatzer (AGA Medical Corporation) (n=80, 48%), Gore Helex (n=48, 29%) and Premere TM (St Jude Medical) (n=38, 23%). One (0.6%) neurological event occurred during follow-up. At 6 months significant residual shunting after Valsalva was highest in the group that received the Helex (58.3%), and lower for Premere (39.5%) and Amplatzer (32.5%). At final follow-up residual shunting remained higher in patients with the Helex (33.3%) than in Premere (18.5%) and Amplatzer (11%). Amplatzer had a significantly lower residual shunt rate than Helex (p<0.05 at 6 months and final follow-up). The Premere had an intermediate residual shunt rate. Septal aneurysm also predicted residual shunting (RR=24.7, 95% CI: 8.2 to 74.4, p<0.0001). CONCLUSIONS: Percutaneous PFO closure is an efficacious progressive treatment but closure rates also depend on the presence of aneurysm and differ between occluders.

Diagnosis and management of elite young athletes undergoing arrhythmia intervention.

BACKGROUND: Sudden cardiac death is the most common cause of mortality in young athletes. In some of these, the final pathway is arrhythmia. The authors aimed to identify the incidence, diagnosis and management of athletes undergoing investigation and intervention for cardiac arrhythmias. METHODS: Retrospective analysis of all patients between 10 and 17 years presenting to a supra-regional paediatric cardiac unit for investigation and intervention for a cardiac arrhythmia. Elite athletes (county and national level) were identified from the departmental clinical and arrhythmia databases (October 1997-2007). Patients with significant congenital heart disease were excluded. RESULTS: From 657 patients undergoing 680 interventions, 324 were excluded. From the remaining 333 we identified 11 elite athletes - football (n=3), martial arts (n=2), rugby (n=2), triple jump, netball, canoeing, and motor sport (n=1). Presenting symptoms included palpitations (n=8) and syncope (n=1). Two were asymptomatic and investigated following routine screening. Diagnoses included atrioventricular (AV) re-entry tachycardia (n=3), AV node re-entry tachycardia (n=4), complete heart block (n=1), sinus node dysfunction (n=1), vasovagal syncope (n=1) and pre-excited atrial fibrillation (n=1). Arrhythmia interventions included implantable loop recorder (n=2), diagnostic electrophysiology study (n=9), including radiofrequency ablation (n=5), cryoablation (n=2) and pacemaker implantation (n=2). Following intervention, 10 children returned to competitive sport. There were no deaths. No child required long-term medication post-intervention. CONCLUSION: Of the young competitive athletes identified from the authors' study, there was a high incidence of significant arrhythmias. Intervention is usually successful and most athletes return to elite sport without the need for long-term medication.

Anomalous right subclavian artery and coarctation-related aneurysm repaired with bilateral subclavian-to-carotid transposition and exclusion stent-grafting.

INTRODUCTION: Aortic arch anomalies are common; however, the presence of concomitant pathology may present a complex management problem. REPORT: A 42 year old lady with anomalous right subclavian artery was found to have recurrent coarctation of the aorta and an aneurysm related to the previous repair. Management of the aneurysm was complicated by the proximity of subclavian artery origins. Bilateral subclavian-to-carotid transposition was undertaken to preserve antegrade vertebral artery flow, with subsequent exclusion stent-grafting of the aneurysm and coarctation. DISCUSSION: This case illustrates combined surgical and interventional radiological repair to deal with a complex thoracic aortic clinical problem.

Functional expression of kinin B1 and B2 receptors in mouse abdominal aorta

Previous studies have shown that the vascular reactivity of the mouse aorta differs substantially from that of the rat aorta in response to several agonists such as angiotensin II, endothelin-1 and isoproterenol. However, no information is available about the agonists bradykinin (BK) and DesArg9BK (DBK). Our aim was to determine the potential expression of kinin B1 and B2 receptors in the abdominal mouse aorta isolated from C57BL/6 mice. Contraction and relaxation responses to BK and DBK were investigated using isometric recordings. The kinins were unable to induce relaxation but concentration-contraction response curves were obtained by applying increasing concentrations of the agonists BK and DBK. These effects were blocked by the antagonists Icatibant and R-715, respectively. The potency (pD2) calculated from the curves was 7.0 ± 0.1 for BK and 7.3 ± 0.2 for DBK. The efficacy was 51 ± 2 percent for BK and 30 ± 1 percent for DBK when compared to 1 æM norepinephrine. The concentration-dependent responses of BK and DBK were markedly inhibited by the arachidonic acid inhibitor indomethacin (1 æM), suggesting a mediation by the cyclooxygenase pathway. These contractile responses were not potentiated in the presence of the NOS inhibitor L-NAME (1 mM) or endothelium-denuded aorta, indicating that the NO pathway is not involved. We conclude that the mouse aorta constitutively contains B1 and B2 subtypes of kinin receptors and that stimulation with BK and DBK induces contractile effect mediated by endothelium-independent vasoconstrictor prostanoids.