Heat Shock Proteins Alterations in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory and autoimmune disease characterized by the attack of the immune system on the body's healthy joint lining and degeneration of articular structures. This disease involves an increased release of inflammatory mediators in the affected joint that sensitize sensory neurons and create a positive feedback loop to further enhance their release. Among these mediators, the cytokines and neuropeptides are responsible for the crippling pain and the persistent neurogenic inflammation associated with RA. More importantly, specific proteins released either centrally or peripherally have been shown to play opposing roles in the pathogenesis of this disease: an inflammatory role that mediates and increases the severity of inflammatory response and/or an anti-inflammatory and protective role that modulates the process of inflammation. In this review, we will shed light on the neuroimmune function of different members of the heat shock protein (HSPs) family and the complex manifold actions that they exert during the course of RA. Specifically, we will focus our discussion on the duality in the mechanism of action of Hsp27, Hsp60, Hsp70, and Hsp90.

Molecular Systematics of the Firefly Genus Luciola (Coleoptera: Lampyridae: Luciolinae) with the Description of a New Species from Singapore.

The firefly genus Luciola sensu McDermott contains 282 species that are distributed across major parts of Asia, Europe, Africa, Australia, and the Pacific islands. Due to phenotypic similarities, species identification using external morphological characters can be unreliable for this group. Consequently, decades of piecemeal taxonomic treatments have resulted in numerous erroneous and contentious classifications. Furthermore, our understanding of the group's evolutionary history is limited due to the lack of a robust phylogenetic framework that has also impeded efforts to stabilize its taxonomy. Here, we constructed molecular phylogenies of Luciola and its allies based on combined mitogenomes and Cytochrome c oxidase subunit 1 (COX1) sequences including a newly sequenced mitogenome of an unidentified taxon from Singapore. Our results showed that this taxon represents a distinct and hitherto undescribed evolutionary lineage that forms a clade with L. filiformis from Japan and L. curtithorax from China. Additionally, the Singaporean lineage can be differentiated from other congeners through several external and internal diagnostic morphological characters, and is thus described herein as a new species. Our phylogeny also strongly supported the paraphyly of Luciola with regard to L. cruciata and L. owadai, which were inferred to be more closely related to the genus Aquatica as opposed to other members of Luciola sensu stricto. The genus Hotaria was inferred as a derived clade within Luciola (sister to L. italica), supporting its status as a subgenus of Luciola instead of a distinct genus. This is the first time since 1909 that a new species of luminous firefly has been discovered in Singapore, highlighting the need for continued biodiversity research, even in small, well-studied and highly developed countries, such as Singapore.

Description of the larva of a firefly species, Pygoluciola dunguna Nada (Coleoptera: Lampyridae).

Pygoluciola dunguna Nada, 2018 was described from Peninsular Malaysia, using males and reliably associated females. This paper details description of the larva which has been conclusively identified as Pygoluciola dunguna based on DNA barcoding technique and uses morphology, brief habitat and behavioural data. A total of 70 larval specimens were measured and their main features described. The larvae exhibit a riparian or semi-aquatic behaviour, observed crawling on the sandy edge of shallow streams. The stake-like projections along the length of the body suggest a form of defensive mechanism from falling prey to aquatic predators.

Association between BCL11A, HSB1L-MYB, and XmnI γG-158 (C/T) gene polymorphism and hemoglobin F level in Egyptian sickle cell disease patients.

Sickle cell disease (SCD) is a monogenic disease characterized by multisystem morbidity and highly variable clinical course. Inter-individual variability in hemoglobin F (HbF) levels is one of the main modifiers that account for the clinical heterogeneity in SCD. HbF levels are affected by, among other factors, single nucleotide polymorphisms (SNPs) at the BCL11A gene and the HBS1L-MYB intergenic region and Xmn1 gene. Our aim was to investigate HbF-enhancer haplotypes at these loci to obtain a first overview of the genetic situation of SCD patients in Egypt and its impact on the severity of the disease. The study included 100 SCD patients and 100 matched controls. Genotyping of BCL11A (rs1886868 C/T), HBS1L-MYB (rs9389268 A/G) and Xmn1 γG158 (rs7842144 C/T) SNPs showed no statistically significant difference between SCD patients and controls except for the hetero-mutant genotypes of BCL11A which was significantly higher in SCD patients compared with controls. Baseline HbF levels were significantly higher in those with co-inheritance of polymorphic genotypes of BCL11A + HSB1L-MYB and BCL11A + Xmn1. Steady-state HbF levels, used as an indicator of disease severity, were significantly higher in SCD-Sß patients having the polymorphic genotypes of HSB1L-MYB. Fold change of HbF in both patient groups did not differ between those harboring the wild and the polymorphic genotypes of the studied SNPs. In conclusion, BCL11A, HSB1L, and Xmn1 genetic polymorphisms had no positive impact on baseline HbF levels solely but had if coexisted. Discovery of the molecular mechanisms controlling HbF production could provide a more effective strategy for HbF induction.

γ-Glutamyltransferase as a Novel Virulence Factor of Acinetobacter baumannii Inducing Alveolar Wall Destruction and Renal Damage in Systemic Disease.

A thorough understanding of Acinetobacter baumannii pathogenicity is the key to identifying novel drug targets. In the current study, we characterize the γ-glutamyltransferase enzyme (GGT) as a novel virulence factor. A GGT assay showed that the enzyme is secreted via the type II secretion system and results in higher extracellular activity for the hypervirulent AB5075 than the laboratory-adapted strain American Type Culture Collection 17978. Enzyme-linked immunosorbent assay revealed that the former secretes larger amounts of GGT, and a rifampicin messenger RNA stability study showed that one reason for this could be the longer AB5075 ggt transcript half-life. Infection models confirmed that GGT is required for the virulence of A. baumannii. Finally, we show that clinical isolates with significantly higher extracellular GGT activity resulted in more severe infections, and assay of immune response and tissue damage markers confirm this correlation. The current findings establish for the first time the role of the GGT in the pathogenicity of A. baumannii.

The Luciolinae of S. E. Asia and the Australopacific region: a revisionary checklist (Coleoptera: Lampyridae) including description of three new genera and 13 new species.

This overview of the Luciolinae addresses the fauna of S. E. Asia including India, Sri Lanka, China, Japan, Malaysia, Thailand, Laos, Cambodia, Vietnam, Indonesia, the Philippines, the Republic of Palau, Federated States of Micronesia, and the Australopacific area of Australia, Papua New Guinea, Solomon Islands, New Caledonia, Vanuatu and Fiji.Of the 28 genera now recognised in the Luciolinae we address 27 genera from the study area as defined above, including three new genera which are described herein, and 222 species including 13 species newly described herein. Photuroluciola Pic from Madagascar is the only Luciolinae genus not addressed here. A key to genera is presented. Keys to species are either included here or referenced in existing literature. Twelve genera have had no new taxonomic decisions made nor are any new species records listed, and are addressed in an abbreviated fashion, with short diagnoses and plates of features of life stages: Aquatica Fu et al. 2010, Australoluciola Ballantyne 2013, Convexa Ballantyne 2009, Emeia Fu et al. 2012a, Inflata Boontop 2015, Lloydiella Ballantyne 2009, Missimia Ballantyne 2009, Pteroptyx Olivier 1902, Pyrophanes Olivier 1885, Sclerotia Ballantyne 2016, Triangulara Pimpasalee 2016, and Trisinuata Ballantyne 2013.                Abscondita Ballantyne 2013 contains 8 species, and includes new records for Abs. anceyi (Olivier 1883), Abs. chinensis (L.) (which is newly synonymised with Luciola succincta Bourgeois), Abs. terminalis (Olivier 1883) including a first record from both Laos and Thailand, and Abs. perplexa (Walker 1858). Luciola pallescens Gorham 1880 is transferred to Abscondita and the pronotal colour range is addressed from a wide range of localities. Abs. berembun Nada sp. nov. and Abs. jerangau Nada sp. nov. are described from Malaysia. Hooked bursa plates are described for pallescens and berembun.                Aquilonia Ballantyne 2009 is expanded to include 3 species. Gilvainsula Ballantyne 2009, represented by two species from the south eastern coast of New Guinea is synonymised under Aquilonia Ballantyne 2009, which is briefly redescribed and keyed from: Aquil. costata (Lea) from northern Australia, including many new records, Aquil. messoria (Ballantyne) comb. nov. and Aquil. similismessoria (Ballantyne) comb. nov.                Asymmetricata Ballantyne 2009 now includes 4 species. As. bicoloripes (Pic 1927) comb. nov. and As. humeralis (Walker 1858) comb. nov. are transferred from Luciola, with L. doriae Olivier 1885, L. impressa Olivier 1910b and L. notatipennis Olivier 1909a newly synonymised with As. humeralis. Luciola aemula Olivier 1891 is synonymised with As. ovalis (Hope 1831). The variation in the extent of the anterior median emargination of the light organ in ventrite 7, and the possibility of a bipartite light organ in males of As. circumdata (Motsch. 1854) is explored. Females of both As. circumdata and As. ovalis (Hope 1831) are without bursa plates and the distinctively shaped median oviduct plate in each is described. Records from Thailand are recorded for both As. circumdata and As. ovalis.                Atyphella Olliff 1890 now contains 28 species with 4 transferred from other genera, and one new species: Aty. abdominalis (Olivier 1886) comb. nov. and Aty. striata (Fabricius 1801) comb. nov. are transferred from Luciola, with Aty. carolinae Olivier 1911b and Aty. rennellia (Ballantyne 2009) comb. nov. transferred from Magnalata Ballantyne 2009. Atyphella telokdalam Ballantyne sp. nov. from Indonesia is described herein. Atyphella is now known from records in the Philippines and Indonesia as well as Australia and New Guinea.                Colophotia Motschulsky 1853 is considered here from seven species for which intact types can be located for three. An abbreviated revision based on the United States National Museum collection only is presented, with specimens of C. bakeri Pic 1924, C. brevis Olivier 1903a, C. plagiata (Erichson 1834) and C. praeusta (Eschscholtz 1822) redescribed, using where possible features of males, females and larvae. Colophotia particulariventris Pic 1938 is newly synonymised with C. praeusta. Colophotia miranda Olivier 1886 and L. truncata Olivier 1886 are treated as species incertae sedis.                Curtos Motschulsky 1845 includes 19 species with suggestions made, but not yet formalised, for the possible transfer of the following seven species from Luciola: Luciola complanata Gorham 1895, L. costata Pic 1929, L. delauneyi Bourgeois 1890, L. deplanata Pic 1929, L. extricans Walker 1858, L. multicostulata Pic 1927 and L. nigripes Gorham 1903. Curtos is not revised here.                Emarginata Ballantyne gen nov. is described for E. trilucida (Jeng et al. 2003b) comb. nov., transferred from Luciola and characterised by the emarginated elytral apex. An extended range of specimens from Thailand is listed.                Kuantana Ballantyne gen. nov. from Selangor, Malaysia is described from K. menayah gen. et sp. nov. having bipartite light organs in ventrite 7 and an asymmetrical tergite 8 which is not emarginated on its left side. Female has no bursa plates.                Luciola Laporte 1833 s. stricto as defined by a population of the type species Luciola italica (L. 1767) from Pisa, Italy, is further expanded and considered to comprise the following19 species: L. antipodum (Bourgeois 1884), L. aquilaclara Ballantyne 2013, L. chapaensis Pic 1923 which is synonymised with L. atripes Pic 1929, L. curtithorax Pic 1928, L. filiformis Olivier 1913c, L. horni Bourgeois 1905, L. hypocrita Olivier 1888, L. italica (L. 1767), L. kagiana Matsumura 1928, L. oculofissa Ballantyne 2013, L. pallidipes Pic 1928 which is synonymised with L. fletcheri Pic 1935, L. parvula Kiesenwetter 1874, L. satoi Jeng Yang 2003, L. tuberculata Yiu 2017, and two species treated as near L. laticollis Gorham 1883, and near L. nicollieri Bugnion 1922. The following are described as new: L. niah Jusoh sp. nov., L. jengai Nada sp. nov. and L. tiomana Ballantyne sp. nov. Luciola niah sp. nov. female has two wide bursa plates on each side of the bursa.                Luciola s. lato (as defined here) consists of 36 species. Twenty-seven species formerly standing under Luciola have been assigned to other genera or synonymised. Seven species are recommended for transfer to Curtos, and 32 species now stand under species incertae sedis.                Magnalata Ballantyne is reduced to the type species M. limbata and redescribed.                Medeopteryx Ballantyne 2013 is expanded to 20 species with the addition of two new combinations, Med. semimarginata (Olivier 1883) comb. nov. and Med. timida (Olivier 1883) comb. nov., both transferred from Luciola, and one new species, Med. fraseri Nada sp. nov. from Malaysia. The range of this genus now extends from Australia and the island of New Guinea to SE Asia. Medeopteryx semimarginata females have wide paired bursa plates.                Pygoluciola Wittmer 1939 now includes 19 species with 5 new species: P. bangladeshi Ballantyne sp. nov., P. dunguna Nada 2018, P. matalangao Ballantyne sp. nov. (scored by the code name 'Jeng Matalanga' in Ballantyne Lambkin 2013), P. phupan Ballantyne sp. nov. and P. tamarat Jusoh sp. nov. Six species are transferred from Luciola: P. abscondita (Olivier 1891) comb. nov., P. ambita (Olivier 1896) comb. nov., P. calceata (Olivier 1905) comb. nov., P. insularis (Olivier 1883) comb. nov., P. nitescens (Olivier 1903b) comb. nov. and P. vitalisi (Pic 1934) comb. nov., and redescribed from males, and includes female reproductive anatomy for P. nitescens comb. nov. and P. dunguna, both of which have hooked bursa plates.                Serratia Ballantyne gen. nov. is erected for S. subuyania gen. et sp. nov. and characterised by the serrate nature of certain antennal flagellar segments in the male.                The following 37 species listed under species incertae sedis are further explored: Colophotia miranda Olivier 1886, Lampyris serraticornis Boisduval 1835, Luciola angusticollis Olivier 1886, L. antennalis Bourgeois 1905, L. antica (Boisduval 1835), L. apicalis (Eschscholtz 1822), L. aurantiaca Pic 1927, L. bicoloriceps Pic 1924, L. binhana Pic 1927, L. bourgeoisi Olivier 1895, L. dilatata Pic 1929, L. exigua (Gyllenhall 1817), L. exstincta Olivier 1886, L. fissicollis Fairmaire 1891, L. flava Pic 1929, L. flavescens (Boisduval 1835), L. fukiensis Pic 1955, L. immarginata Bourgeois 1890, L. incerta (Boisduval 1835), L. infuscata (Erichson 1834), L. intricata (Walker 1858), L. japonica (Thunberg 1784), L. klapperichi Pic 1955, L. lata Olivier 1883, L. limbalis Fairmaire 1889, L. marginipennis (Boisduval 1835), L. melancholica Olivier 1913a, L. robusticeps Pic 1928, L. ruficollis (Boisduval 1835), L. spectralis Gorham 1880, L. stigmaticollis Fairmaire 1887, L. tincticollis Gorham 1895, L. trivandrensis Raj 1947, L. truncata Olivier 1886, L. vittata (Laporte 1833) Pteroptyx atripennis Pic 1923 and P. curticollis Pic 1923.                While phylogenetic analyses indicate their distinctiveness, no further taxonomic action is taken with Luciola cruciata Motschulsky 1854 and L. owadai Sâtô et Kimura 1994 from Japan given the importance of the former as a national icon. Analyses also indicate that Lampyroidea syriaca Costa 1875 belongs in Luciola s. str. A much wider taxonomic analysis of this genus including all the species is necessary before any further action can be taken.

Prevalence, clinical characteristics, and predictors of peripheral arterial disease in hemodialysis patients: a cross-sectional study.

BACKGROUND: Peripheral arterial disease (PAD) is common in patients with end-stage renal disease on hemodialysis, but is frequently underdiagnosed. The risk factors for PAD are well known within the general population, but they differ somewhat in hemodialysis patients. This study aimed to determine the prevalence of PAD and its risk factors in patients on hemodialysis. METHODS: This cross-sectional study included 156 hemodialysis patients. Comorbidities and laboratory parameters were analyzed. Following clinical examinations, the ankle-brachial index was measured in all patients. PAD was diagnosed based on the clinical findings, ankle-brachial index < 0.9, and PAD symptoms. RESULTS: PAD was present in 55 of 156 (35.3%; 95% CI, 27.7-42.8%) patients. The patients with PAD were significantly older (67 ± 10 years vs. 62 ± 11 years, p = 0.014), more likely to have diabetes mellitus (p = 0.022), and anemia (p = 0.042), and had significantly lower serum albumin (p = 0.005), total cholesterol (p = 0.024), and iron (p = 0.004) levels, higher glucose (p = 0.002) and C-reactive protein (p < 0.001) levels, and lower dialysis adequacies (p = 0.040) than the patients without PAD. Multivariate analysis showed higher C-reactive protein level (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.00-1.06; p = 0.030), vascular access by Hickman catheter (OR, 4.66; 95% CI, 1.03-21.0; p = 0.045), and symptoms of PAD (OR, 5.20; 95% CI, 2.60-10.4; p < 0.001) as independent factors associated with PAD in hemodialysis patients. CONCLUSION: The prevalence of PAD was high among patients with end-stage renal disease on hemodialysis. Symptoms of PAD, higher C-reactive protein levels, and Hickman vascular access were independent predictors of PAD in patients on hemodialysis.

Comparative proteomics analyses of Acinetobacter baumannii strains ATCC 17978 and AB5075 reveal the differential role of type II secretion system secretomes in lung colonization and ciprofloxacin resistance.

Acinetobacter baumannii is an emerging nosocomial pathogen with alarming antibiotic resistance profiles. A better understanding of the virulence and resistance mechanisms of this pathogen is necessary for identifying new methods to combat its infections in a more efficient way. In this regard, the type II secretion system (T2SS) of A. baumannii is an attractive target majorly secreting lipid-metabolizing enzymes and contributes significantly to its virulence. No attempts have been made to study the differential role, and the nature of T2SS secreted proteins among different strains of A. baumannii. In this study, we compare T2SS substrates and functions between A. baumannii strains ATCC 17978, and the MDR highly virulent strain AB5075. The functional categories of the T2-secreted proteins were analyzed, and the virulence potential of the tested strains was compared in vivo using a murine pneumonia model. Biofilm formation was compared using crystal violet assay in micro-titer plates. The contribution to antibiotic resistance was measured by determining the minimum inhibitory concentration (MIC) of different classes of antibiotic. Results indicate that the T2SS secretome gives a colonization advantage to AB5075 over ATCC 1797 but is more important for biofilm formation by the latter. Transposon insertional inactivation of the general secretory pathway protein D (gspD), which is a key component in the structure of the T2SS, significantly increased the MIC of AB5075 to ciprofloxacin. Our report is the first to describe the strain-dependent evolution of the T2SS secretome in relation to the virulence and antibiotic resistance attributes of Gram-negative species.

A new species of Pygoluciola Wittmer with unusual abdominal configuration, from lowland dipterocarp forest in Peninsular Malaysia (Coleoptera: Lampyridae: Luciolinae).

A new species of firefly (Coleoptera: Lampyridae) Pygoluciola dunguna Nada sp. nov. is described from males and reliably associated females, collected mainly from lowland dipterocarp forests of Peninsular Malaysia at elevations below 300 m a.s.l. This species is found to be terrestrial, flying at low heights between 10-15 m above ground in between the herbaceous plants. Males are intermediate between the two types of Pygoluciola Wittmer known until now. A list of species, and a key to males and known females of Pygoluciola is given. The female bursa has paired elongate hook like bursa plates.

Targeting α-synuclein as a therapeutic strategy for Parkinson's disease.

INTRODUCTION: α-Synuclein, a neuronal protein, plays a central role in the pathophysiology of Parkinson's disease (PD), the second most prevalent neurodegenerative disorder. Cases of PD have increased tremendously over the past decade necessitating the identification of new therapeutic targets to reduce patient morbidity and to improve PD patients' quality of life. AREAS COVERED: The purpose of this article is to provide an update on the role of α-synuclein in fibrils formation and review its role as an effective immunotherapeutic target for PD. The rapidly expanding evidence for the contribution of α-synuclein to the pathogenesis of PD led to the development of antibodies against the C terminus of α-synuclein and other molecules involved in the inflammatory signaling pathways that were found to contribute significantly to initiation and progression of the disease. EXPERT OPINION: The readers will obtain new insights on the mechanisms by which α-synuclein can trigger the development of PD and other related degenerative disorders along with the potential role of active and passive antibodies targeted against specific form of α-synuclein aggregates to clear neurotoxicity, stop the propagation of the prion-like behavior of these oligomers and reverse neuronal degeneration associated with PD.

Ventricular tachycardia from intracardiac hematoma in the setting of blunt thoracic trauma.

In the victims of motor vehicle accidents, unrecognized myocardial injuries may pose diagnostic and therapeutic challenges. Herein, we present a case of a 17-year-old man who developed multiple ventricular premature complexes and nonsustained ventricular tachycardia in the setting of blunt chest trauma from a motor vehicle accident. We discuss significance of the electrocardiographic abnormalities in making an accurate diagnosis of cardiac hematoma and its management.

Outcome of pulmonary vein isolation ablation for paroxysmal atrial fibrillation: predictive role of left atrial mechanical dyssynchrony by speckle tracking echocardiography.

INTRODUCTION: Although few clinical variables have been associated with recurrence of atrial fibrillation (AF) after pulmonary vein isolation (PVI) the role of left atrial (LA) mechanical function in the outcome of catheter ablation of AF is not adequately defined. The aim of our study was to determine whether LA mechanical dyssynchrony as evaluated by speckle tracking echocardiography can predict outcome of PVI ablation procedure in patients with paroxysmal AF. METHODS: Twenty-five patients (age 58 ± 11 years, [mean ± standard deviation], 17 males) with paroxysmal AF who met specific enrollment criteria pertaining to clinical presentation and follow-up, assessment of LA mechanical dyssynchrony, and strategy of catheter ablation procedure were enrolled. For LA mechanical dyssynchrony assessment, the time to peak longitudinal strain (TPk) in opposing walls in the midportion of the LA walls at peak atrial contraction in standard two- and four-chamber echocardiographic views by vector velocity imaging (VVI) was measured. Outcome of PVI procedure, whether no recurrence (NR) or AF recurrence (AFR) after 3 months of post-procedural blanking period, was evaluated based on AF-related symptoms and documentation of AF by electrocardiogram, continuous 24-h Holter, and intermittent event monitor recordings. RESULTS: During a follow-up period of 20.3 ± 8.6 months, 18 out of 25 (72 %) patients had no recurrence (NR group), and 7 out of 25 (28 %) patients had recurrence of AF (AFR group). Significant gender difference was observed in terms of outcome such that all AFR patients were men and no woman had recurrence of AF. Between the NR and AFR groups, neither the left atrial diameter, 4.0 ± 0.3 and 4.2 ± 0.2 cm, respectively (p = 0.2), nor the left atrial volume indexes, 45 ± 15 and 48 ± 20 ml/m(2), respectively (p = 0.56), were statistically significantly different. For LA mechanical function, compared to the patients in NR group who had maximum opposing wall TPk delay of 39.9 ± 12.0 ms, those in the AFR group demonstrated significantly more LA mechanical dyssynchrony with maximum opposing wall TPk delay of 64.4 ± 17.0 ms prior to ablation (p = 0.007). Using receiver operative characteristic analyses of the data that had an area under the curve of 0.865, we identified a maximum opposing wall delay cutoff value of 51 ms which predicted AF recurrence with sensitivity and specificity values of 89 and 72 %, respectively (p = 0.005). CONCLUSIONS: Speckle tracking strain analysis echocardiography can evaluate the LA mechanical dyssynchrony quantitatively. The severity of LA mechanical dyssynchrony by VVI can predict the outcome of PVI catheter ablation for paroxysmal AF.

Speech-induced atrial tachycardia: an unusual presentation of supraventricular tachycardia.

A 63-year-old male radio announcer was admitted with a narrow complex, long RP tachycardia. While in the awake state, the patient spoke in his radio voice, initiating and maintaining the tachycardia. Three-dimensional electroanatomic mapping during electrophysiology study localized the tachycardia to the ostium of the right superior pulmonary vein. After single radiofrequency energy application, no further arrhythmias were inducible with speech. At more than 1 year of follow-up, the patient had no recurrences and continues to work as a radio announcer.

Rhizopus-associated soft tissue infection in an immunocompetent air-conditioning technician after a road traffic accident: a case report and review of the literature.

Rhinocerebral or sinopulmonary mucromycosis is a well-recognized human fungal infection found among immunocompromised and diabetic patients. However, the infection is rare among immunocompetent hosts. We are reporting the case of an adult immunocompetent male patient working as an air-conditioning technician. The patient was a victim of a road traffic accident (RTA) and sustained multiple fractures in the proximal part of the left tibia, distal femur, and scapula. Two weeks postoperatively, Rhizopus microspores were isolated from an infected traumatic wound over the distal femur. Surgical debridement was performed, and the patient was started on amphotericin B. Occupational exposure history and workplace environmental sanitation are crucial for the prevention of this potentially fatal yet preventable infection.

Ventricular arrhythmias and acute left ventricular dysfunction as a primary and life-threatening manifestation of a mitochondrial crisis: A novel management strategy.

Mitochondrial disorders are genetic diseases that result in a deficiency of energy metabolism (ATP production). A "mitochondrial crisis" can occur in the setting of infection, dehydration, or physiologic stress. The hallmark of a mitochondrial crisis is failure of multiple individual organ systems. The mortality of mitochondrial crisis is high and therapy is supportive but involves a specific strategy of hydration with dextrose-containing IV fluids, avoidance of many medications known to worsen mitochondrial function, and limitations of oxygenation as this can promote free radical production. We report a case of a patient with known mitochondrial disease that presented with a mitochondrial crisis with prominent and life-threatening cardiac manifestations including long QT, ventricular arrhythmias, and acute left ventricular systolic dysfunction in addition to rhabdomyolysis, lactic acidosis, and an acute kidney injury. This patient was managed successfully with a specifically tailored supportive strategy, a high-dose metabolic cocktail, permissive hypoxia, and low-protein diet. At 10 weeks post discharge all electrocardiographic abnormalities resolved and ventricular recovery has been observed. Given the increased survival of this population of patients into adulthood it is important that these adjunctive therapeutic strategies require consideration by clinicians treating this group of patients.

Role of the Na+-K+-2Cl- cotransporter in the development of capsaicin-induced neurogenic inflammation.

Recent behavioral and electrophysiological studies have attributed an important role to dorsal root reflexes (DRRs) in the initiation and development of neurogenic inflammation produced by intradermal capsaicin (CAP). The DRRs can occur in peptidergic fibers, resulting in peripheral release of neuromediators that produce vasodilation, plasma extravasation and subsequently hyperalgesia and allodynia. In this study, we have evaluated the effect of spinal administration of bumetanide (a blocker of the Na+-K+-2Cl- cotransporter, NKCC) on DRR activity, changes in cutaneous blood flow (vasodilation), hindpaw edema, mechanical allodynia, and hyperalgesia induced by intradermal injection of 1% CAP in Sprague-Dawley rats. Vasodilation was monitored using laser Doppler flowmetry, neurogenic edema was evaluated by measurements of hindpaw volume, and secondary mechanical allodynia and hyperalesia were tested using von Frey filaments (10 and 200 mN) applied to the plantar surface of the paw. Changes in the blood flow were blocked significantly by intrathecal bumetanide at 10 and 100 microM in both pre- and posttreatment studies. Spinal bumetanide at 10 and 100 microM blocked neurogenic edema when it was administered before CAP injection, but only bumetanide at 100 microM administered after CAP injection reduced the paw edema significantly. Furthermore, the administration of bumetanide onto the spinal cord reduced the increment in DRR activity produced by CAP. Finally, both secondary mechanical allodynia and hyperalesia were reduced by bumetanide at 1, 10, and 100 microM. Taken together these results suggest that NKCC is involved in the increases in DRR activity, neurogenic inflammation and hyperalgesia and allodynia induced by intradermal CAP.