bluuebunny/crossref_metadata_2025 huggingface dataset:
Oropouche Virus Infection and Pathogenesis Are Restricted by MAVS, IRF-3, IRF-7, and Type I Interferon Signaling Pathways in Nonmyeloid Cells
Authors: Proenca-Modena Jose Luiz , Sesti-Costa Renata , Pinto Amelia K. , Richner Justin M. , Lazear Helen M. , Lucas Tiffany , Hyde Jennifer L. , Diamond Michael S.
Published: February 2015

Oropouche virus (OROV) is a member of the
Orthobunyavirus
genus in the
Bunyaviridae
family and a prominent cause of insect-transmitted viral disease in Central and South America. Despite its clinical relevance, little is known about OROV pathogenesis. To define the host defense pathways that control OROV infection and disease, we evaluated OROV pathogenesis and immune responses in primary cells and mice that were deficient in the RIG-I-like receptor signaling pathway (MDA5, RIG-I, or MAVS), downstream regulatory transcription factors (IRF-3 or IRF-7), beta interferon (IFN-β), or the receptor for type I IFN signaling (IFNAR). OROV replicated to higher levels in primary fibroblasts and dendritic cells lacking MAVS signaling, the transcription factors IRF-3 and IRF-7, or IFNAR than in wild-type (WT) cells. In mice, deletion of IFNAR, MAVS, or IRF-3 and IRF-7 resulted in uncontrolled OROV replication, hypercytokinemia, extensive liver damage, and death, whereas WT congenic animals failed to develop disease. Unexpectedly, mice with a selective deletion of IFNAR on myeloid cells (CD11c Cre
+
Ifnar
f/f
or LysM Cre
+
Ifnar
f/f
) did not sustain enhanced disease with OROV or a selective (flox/flox) deletion La Crosse virus, a closely related encephalitic orthobunyavirus. In bone marrow chimera studies, recipient irradiated
Ifnar
−/−
mice reconstituted with WT hematopoietic cells sustained high levels of OROV replication and liver damage, whereas WT mice reconstituted with
Ifnar
−/−
bone marrow were resistant to disease. Collectively, these results establish a dominant protective role for MAVS, IRF-3 and IRF-7, and IFNAR in restricting OROV infection and tissue injury and suggest that IFN signaling in nonmyeloid cells contributes to the host defense against orthobunyaviruses.

IMPORTANCE
Oropouche virus (OROV) is an emerging arthropod-transmitted orthobunyavirus that causes episodic outbreaks of a debilitating febrile illness in humans in countries of South and Central America. The continued expansion of the range and number of its arthropod vectors increases the likelihood that OROV will spread into new regions. At present, the pathogenesis of OROV in humans or other vertebrate animals remains poorly understood. To define cellular mechanisms of control of OROV infection, we performed infection studies in a series of primary cells and mice that were deficient in key innate immune genes involved in pathogen recognition and control. Our results establish that a MAVS-dependent type I IFN signaling pathway has a dominant role in restricting OROV infection and pathogenesis
in vivo
.
A Role for 3-
O
-Sulfated Heparan Sulfate in Promoting Human Cytomegalovirus Infection in Human Iris Cells
Authors: Baldwin John , Maus Erika , Zanotti Brian , Volin Michael V. , Tandon Ritesh , Shukla Deepak , Tiwari Vaibhav
Published: February 2015

Human cytomegalovirus (HCMV) has emerged as a clinically opportunistic pathogen that targets multiple types of ocular cells and tissues, including the iris region of the uveal tract during anterior uveitis. In this report, we used primary cultures of human iris stroma (HIS) cells derived from human eye donors to investigate HCMV entry. The following lines of evidence suggested the role of 3-
O
-sulfated heparan sulfate (3-
O
S HS) during HCMV-mediated entry and cell-to-cell fusion in HIS cells. First, 3-
O
-sulfotransferase-3 (3-
O
ST-3) expression in HIS cells promoted HCMV internalization, while pretreatment of HIS cells with heparinase enzyme or with anti-3-
O
S HS (G2) peptide significantly reduced the HCMV-mediated formation of plaques/foci. Second, coculture of the HCMV-infected HIS cells with CHO-K1 cells expressing 3-
O
S HS significantly enhanced cell fusion. Finally, a similar trend of enhanced fusion was observed with cells expressing HCMV glycoproteins (gB, gO, and gH-gL) cocultured with 3-
O
S HS cells. Taken together, these results highlight the role of 3-
O
S HS during HCMV plaque formation and cell-to-cell fusion and identify a novel target for future therapeutic interventions.
Cellular STAT3 Functions via PCBP2 To Restrain Epstein-Barr Virus Lytic Activation in B Lymphocytes
Authors: Koganti Siva , Clark Carissa , Zhi Jizu , Li Xiaofan , Chen Emily I. , Chakrabortty Sharmistha , Hill Erik R. , Bhaduri-McIntosh Sumita
Published: February 2015

A major hurdle to killing Epstein-Barr virus (EBV)-infected tumor cells using oncolytic therapy is the presence of a substantial fraction of EBV-infected cells that does not support the lytic phase of EBV despite exposure to lytic cycle-promoting agents. To determine the mechanism(s) underlying this refractory state, we developed a strategy to separate lytic from refractory EBV-positive (EBV
+
) cells. By examining the cellular transcriptome in separated cells, we previously discovered that high levels of host STAT3 (signal transducer and activator of transcription 3) curtail the susceptibility of latently infected cells to lytic cycle activation signals. The goals of the present study were 2-fold: (i) to determine the mechanism of STAT3-mediated resistance to lytic activation and (ii) to exploit our findings to enhance susceptibility to lytic activation. We therefore analyzed our microarray data set, cellular proteomes of separated lytic and refractory cells, and a publically available STAT3 chromatin immunoprecipitation sequencing (ChIP-Seq) data set to identify cellular PCBP2 [poly(C)-binding protein 2], an RNA-binding protein, as a transcriptional target of STAT3 in refractory cells. Using Burkitt lymphoma cells and EBV
+
cell lines from patients with hypomorphic
STAT3
mutations, we demonstrate that single cells expressing high levels of PCBP2 are refractory to spontaneous and induced EBV lytic activation, STAT3 functions via cellular PCBP2 to regulate lytic susceptibility, and suppression of PCBP2 levels is sufficient to increase the number of EBV lytic cells. We expect that these findings and the genome-wide resources that they provide will accelerate our understanding of a longstanding mystery in EBV biology and guide efforts to improve oncolytic therapy for EBV-associated cancers.

IMPORTANCE
Most humans are infected with Epstein-Barr virus (EBV), a cancer-causing virus. While EBV generally persists silently in B lymphocytes, periodic lytic (re)activation of latent virus is central to its life cycle and to most EBV-related diseases. However, a substantial fraction of EBV-infected B cells and tumor cells in a population is refractory to lytic activation. This resistance to lytic activation directly and profoundly impacts viral persistence and the effectiveness of oncolytic therapy for EBV
+
cancers. To identify the mechanisms that underlie susceptibility to EBV lytic activation, we used host gene and protein expression profiling of separated lytic and refractory cells. We find that STAT3, a transcription factor overactive in many cancers, regulates PCBP2, a protein important in RNA biogenesis, to regulate susceptibility to lytic cycle activation signals. These findings advance our understanding of EBV persistence and provide important leads on devising methods to improve viral oncolytic therapies.
Activation of NF-κB by Human Papillomavirus 16 E1 Limits E1-Dependent Viral Replication through Degradation of E1
Authors: Nakahara Tomomi , Tanaka Katsuyuki , Ohno Shin-ichi , Egawa Nagayasu , Yugawa Takashi , Kiyono Tohru
Published: February 2015

NF-κB is a family of transcription factors that regulate gene expression involved in many processes, such as the inflammatory response and cancer progression. Little is known about associations of NF-κB with the human papillomavirus (HPV) life cycle. We have developed a tissue culture system to conditionally induce E1-dependent replication of the human papillomavirus 16 (HPV16) genome in human cervical keratinocytes and found that expression of HPV16 E1, a viral helicase, results in reduction of IκBα and subsequent activation of NF-κB in a manner dependent on helicase activity. Exogenous expression of a degradation-resistant mutant of IκBα, which inhibits the activation of NF-κB, enhanced E1-dependent replication of the viral genome. Wortmannin, a broad inhibitor of phosphoinositide 3-kinases (PI3Ks), and, to a lesser extent, VE-822, an ATR kinase inhibitor, but not KU55933, an ATM kinase inhibitor, suppressed the activation of NF-κB and augmented E1-dependent replication of the HPV16 genome. Interestingly, the enhancement of E1-dependent replication of the viral genome was associated with increased stability of E1 in the presence of wortmannin as well as the IκBα mutant. Collectively, we propose that expression of E1 induces NF-κB activation at least in part through the ATR-dependent DNA damage response and that NF-κB in turn limits E1-dependent replication of HPV16 through degradation of E1, so that E1 and NF-κB may constitute a negative feedback loop.

IMPORTANCE
A major risk factor in human papillomavirus (HPV)-associated cancers is persistent infection with high-risk HPVs. To eradicate viruses from infected tissue, it is important to understand molecular mechanisms underlying the establishment and maintenance of persistent infection. In this study, we obtained evidence that human papillomavirus 16 (HPV16) E1, a viral DNA helicase essential for amplification of the viral genomes, induces NF-κB activation and that this limits E1-dependent genome replication of HPV16. These results suggest that NF-κB mediates a negative feedback loop to regulate HPV replication and that this feedback loop could be associated with control of the viral copy numbers. We could thus show for the first time that NF-κB activity is involved in the establishment and maintenance of persistent HPV infection.
Human Papillomavirus 16 Oncoprotein Expression Is Controlled by the Cellular Splicing Factor SRSF2 (SC35)
Authors: McFarlane Melanie , MacDonald Alasdair I. , Stevenson Andrew , Graham Sheila V.
Published: February 2015

High-risk human papillomaviruses (HR-HPV) cause anogenital cancers, including cervical cancer, and head and neck cancers. Human papillomavirus 16 (HPV16) is the most prevalent HR-HPV. HPV oncogenesis is driven by two viral oncoproteins, E6 and E7, which are expressed through alternative splicing of a polycistronic RNA to yield four major splice isoforms (E6 full length, E6*I, E6*II, E6*X). The production of multiple mRNA isoforms from a single gene is controlled by serine/arginine-rich splicing factors (SRSFs), and HPV16 infection induces overexpression of a subset of these, SRSFs 1, 2, and 3. In this study, we examined whether these proteins could control HPV16 oncoprotein expression. Small interfering RNA (siRNA) depletion experiments revealed that SRSF1 did not affect oncoprotein RNA levels. While SRSF3 knockdown caused some reduction in E6E7 expression, depletion of SRSF2 resulted in a significant loss of E6E7 RNAs, resulting in reduced levels of the E6-regulated p53 proteins and E7 oncoprotein itself. SRSF2 contributed to the tumor phenotype of HPV16-positive cervical cancer cells, as its depletion resulted in decreased cell proliferation, reduced colony formation, and increased apoptosis. SRSF2 did not affect transcription from the P
97
promoter that controls viral oncoprotein expression. Rather, RNA decay experiments showed that SRSF2 is required to maintain stability of E6E7 mRNAs. These data show that SRSF2 is a key regulator of HPV16 oncoprotein expression and cervical tumor maintenance.

IMPORTANCE
Expression of the HPV16 oncoproteins E7 and E6 drives HPV-associated tumor formation. Although increased transcription may yield increased levels of E6E7 mRNAs, it is known that the RNAs can have increased stability upon integration into the host genome. SR splicing factors (SRSFs) control splicing but can also control other events in the RNA life cycle, including RNA stability. Previously, we demonstrated increased levels of SRSFs 1, 2, and 3 during cervical tumor progression. Now we show that SRSF2 is required for expression of E6E7 mRNAs in cervical tumor but not nontumor cells and may act by inhibiting their decay. SRSF2 depletion in W12 tumor cells resulted in increased apoptosis, decreased proliferation, and decreased colony formation, suggesting that SRSF2 has oncogenic functions in cervical tumor progression. SRSF function can be targeted by known drugs that inhibit SRSF phosphorylation, suggesting a possible new avenue in abrogating HPV oncoprotein activity.
The Cellobiose Sensor CebR Is the Gatekeeper of Streptomyces scabies Pathogenicity
Authors: Francis Isolde M. , Jourdan Samuel , Fanara Steven , Loria Rosemary , Rigali Sébastien
Published: February 2015

A relatively small number of species in the large genus Streptomyces are pathogenic; the best characterized of these is Streptomyces scabies. The pathogenicity of S. scabies strains is dependent on the production of the nitrated diketopiperazine thaxtomin A, which is a potent plant cellulose synthesis inhibitor. Much is known about the genetic loci associated with plant virulence; however, the molecular mechanisms by which S. scabies triggers expression of thaxtomin biosynthetic genes, beyond the pathway-specific activator TxtR, are not well understood. In this study, we demonstrate that binding sites for the cellulose utilization repressor CebR occur and function within the thaxtomin biosynthetic cluster. This was an unexpected result, as CebR is devoted to primary metabolism and nutritive functions in nonpathogenic streptomycetes. In S. scabies, cellobiose and cellotriose inhibit the DNA-binding ability of CebR, leading to an increased expression of the thaxtomin biosynthetic and regulatory genestxtA,txtB, andtxtR. Deletion ofcebRresults in constitutive thaxtomin A production and hypervirulence of S. scabies. The pathogenicity of S. scabies is thus under dual direct positive and negative transcriptional control where CebR is the cellobiose-sensing key that locks the expression oftxtR, the key necessary to unlock the production of the phytotoxin. Interestingly, CebR-binding sites also lie upstream of and within the thaxtomin biosynthetic clusters in Streptomyces turgidiscabies and Streptomyces acidiscabies, suggesting that CebR is most likely an important regulator of virulence in these plant-pathogenic species as well.

IMPORTANCEWhat makes a microorganism pathogenic is not limited to the genes acquired for virulence. Using the main causative agent of scab lesions on root and tuber crops as an example, our work identified the subtle but essential genetic changes that generate thecis-acting elements necessary for proper timing of the expression of the cluster of genes responsible for the biosynthesis of thaxtomin A, the primary virulence factor in plant-pathogenic streptomycetes. These data illustrate a situation in which a regulator associated with primary metabolism in nonpathogens, CebR, has been coopted as a master regulator of virulence in pathogenic species. Furthermore, the manipulation of CebR-mediated control of thaxtomin production will facilitate overproduction of this natural and biodegradable herbicide for commercial purposes. Our work thus provides a concrete example of how a strictly theoretical and computational work was able to elucidate a regulatory mechanism associated with the virulence of a plant pathogen and to generate solutions to purely agro-industrial concerns.
Positioning the Flagellum at the Center of a Dividing Cell To Combine Bacterial Division with Magnetic Polarity
Authors: Lefèvre Christopher T. , Bennet Mathieu , Klumpp Stefan , Faivre Damien
Published: February 2015

Faithful replication of all structural features is a
sine qua non
condition for the success of bacterial reproduction by binary fission. For some species, a key challenge is to replicate and organize structures with multiple polarities. Polarly flagellated magnetotactic bacteria are the prime example of organisms dealing with such a dichotomy; they have the challenge of bequeathing two types of polarities to their daughter cells: magnetic and flagellar polarities. Indeed, these microorganisms align and move in the Earth's magnetic field using an intracellular chain of nano-magnets that imparts a magnetic dipole to the cell. The paradox is that, after division occurs in cells, if the new flagellum is positioned opposite to the old pole devoid of a flagellum during cell division, the two daughter cells will have opposite magnetic polarities with respect to the positions of their flagella. Here we show that magnetotactic bacteria of the class
Gammaproteobacteria
pragmatically solve this problem by synthesizing a new flagellum at the division site. In addition, we model this particular structural inheritance during cell division. This finding opens up new questions regarding the molecular aspects of the new division mechanism, the way other polarly flagellated magnetotactic bacteria control the rotational direction of their flagella, and the positioning of organelles.

IMPORTANCE
Magnetotactic bacteria produce chains of magnetic nanoparticles that endow the cells with a magnetic dipole, a “compass” used for navigation. This feature, however, also drastically complicates cellular division in the case of polarly flagellated bacteria. In this case, the bacteria have to pass on to their daughter cells two types of cellular polarities simultaneously, their magnetic polarity and the polarity of their motility apparatus. We show here that magnetotactic bacteria of the
Gammaproteobacteria
class pragmatically solve this problem by synthesizing the new flagellum at the division site, a division scheme never observed so far in bacteria. Even though the molecular mechanisms behind this scheme cannot be resolved at the moment due to the lack of genetic tools, this discovery provides a new window into the organizational complexity of simple organisms.
Pseudomonas aeruginosa-Induced Bleb-Niche Formation in Epithelial Cells Is Independent of Actinomyosin Contraction and Enhanced by Loss of Cystic Fibrosis Transmembrane-Conductance Regulator Osmoregulatory Function
Authors: Jolly Amber L. , Takawira Desire , Oke Olufolarin O. , Whiteside Sarah A. , Chang Stephanie W. , Wen Emily R. , Quach Kevin , Evans David J. , Fleiszig Suzanne M. J.
Published: February 2015

The opportunistic pathogen
Pseudomonas aeruginosa
can infect almost any site in the body but most often targets epithelial cell-lined tissues such as the airways, skin, and the cornea of the eye. A common predisposing factor is cystic fibrosis (CF), caused by defects in the cystic fibrosis transmembrane-conductance regulator (CFTR). Previously, we showed that when P. aeruginosa enters epithelial cells it replicates intracellularly and occupies plasma membrane blebs. This phenotype is dependent on the type 3 secretion system (T3SS) effector ExoS, shown by others to induce host cell apoptosis. Here, we examined mechanisms for P. aeruginosa-induced bleb formation, focusing on its relationship to apoptosis and the CFTR. The data showed that P. aeruginosa-induced blebbing in epithelial cells is independent of actin contraction and is inhibited by hyperosmotic media (400 to 600 mOsM), distinguishing bacterially induced blebs from apoptotic blebs. Cells with defective CFTR displayed enhanced bleb formation upon infection, as demonstrated using bronchial epithelial cells from a patient with cystic fibrosis and a CFTR inhibitor, CFTR(Inh)-172. The defect was found to be correctable either by incubation in hyperosmotic media or by complementation with CFTR (pGFP-CFTR), suggesting that the osmoregulatory function of CFTR counters P. aeruginosa-induced bleb-niche formation. Accordingly, and despite their reduced capacity for bacterial internalization, CFTR-deficient cells showed greater bacterial occupation of blebs and enhanced intracellular replication. Together, these data suggest that P. aeruginosa bleb niches are distinct from apoptotic blebs, are driven by osmotic forces countered by CFTR, and could provide a novel mechanism for bacterial persistence in the host.

IMPORTANCE
Pseudomonas aeruginosa
is an opportunistic pathogen problematic in hospitalized patients and those with cystic fibrosis (CF). Previously, we showed that P. aeruginosa can enter epithelial cells and replicate within them and traffics to the membrane blebs that it induces. This “bleb-niche” formation requires ExoS, previously shown to cause apoptosis. Here, we show that the driving force for bleb-niche formation is osmotic pressure, differentiating P. aeruginosa-induced blebs from apoptotic blebs. Either CFTR inhibition or CFTR mutation (as seen in people with CF) causes P. aeruginosa to make more bleb niches and provides an osmotic driving force for blebbing. CFTR inhibition also enhances bacterial occupation of blebs and intracellular replication. Since CFTR is targeted for removal from the plasma membrane when P. aeruginosa invades a healthy cell, these findings could relate to pathogenesis in both CF and healthy patient populations.
Management of intestinal failure in children
Authors: Dalzell A Mark
Published: February 2015

The management of children with intestinal failure is a rewarding but resource intensive process. There is however variability in practice and outcome for patients, despite the basic principles of care and measures of success being well defined. The importance of multidisciplinary working is paramount and there is an urgent need to obtain collaboration between paediatric surgical and medical gastroenterological colleagues and an obligation of commissioners to see that there is recognition and implementation of ideal practice as an essential element in improving the outlook for children with intestinal failure in the United Kingdom.
Surgical repair of a rupture of the pectoralis major muscle
Authors: Pochini Alberto De Castro , Andreoli Carlos Vicente , Ejnisman Benno , Maffulli Nicola
Published: February 2015

Muscle rupture is rarely treated surgically. Few reports of good outcomes after muscular suture have been published. Usually, muscular lesions or partial ruptures heal with few side effects or result in total recovery. We report a case of an athlete who was treated surgically to repair a total muscular rupture in the pectoralis major muscle. After 6 months, the athlete returned to competitive practice. After a 2-year follow-up, the athlete still competes in skateboard championships.
The association of cholinergic and cold-induced urticaria: diagnosis and management
Authors: Torabi Bahar , Ben-Shoshan Moshe
Published: February 2015

Physical urticaria is often challenging to diagnose and manage. We present a case of both cholinergic and cold-induced urticaria and discuss the diagnosis and management strategies of these two important conditions.
Thompson and Hamilton type IV Freiberg's disease with involvement of multiple epiphyses of both feet
Authors: Lui Tun Hing
Published: February 2015

A 17-year-old boy reported left second and third toe pain after axial loading injury to his left foot. Radiographs showed collapse of the second metatarsal heads and epiphysial irregularities of the fifth metatarsal heads and the condyle of the proximal phalanx of the hallux of both feet. The patient was diagnosed to have Thompson and Hamilton type IV Freiberg's disease. He was screened for epiphysial dysplasia of the other sites. He had on and off bilateral hip and knee pain. Radiographs showed bilateral symmetrical epiphysial abnormalities with morphological change as focal concavity in bilateral femoral heads and fragmentation of the patellar articular surface with preservation of the patellofemoral joint space.
Flat trachea syndrome: a rare condition with symptoms similar to obstructive airway disease
Authors: Gani Mohammed Akil D , Rogers Vanessa J C , Sachak Khalid H , Marzouk Joseph F K
Published: February 2015

Flat trachea syndrome, commonly known as ‘tracheobronchomalacia’, is a central airway disease characterised by excessive expiratory collapse of the tracheobronchial posterior membrane due to weakness in the airway walls. Patients present with symptoms such as chronic cough, dyspnoea and recurrent respiratory tract infections, which are often attributed to more common conditions such as asthma and chronic obstructive pulmonary disease (COPD). The term ‘Flat Trachea Syndrome’ was first proposed by Niranjan and Marzouk in 2010 following a retrospective study of 28 patients with the condition who underwent surgery for it. The authors advocated the term due to the primary abnormality being collapse of the posterior membranous wall of the central airways as opposed to softening of the tracheal cartilage (tracheobronchomalacia), which they proposed is a misnomer. We present a rare case of a patient with flat trachea syndrome on a history of COPD who initially presented with recurrent respiratory tract infections.
An unusual cause of abdominal distension: intraperitoneal bladder perforation secondary to intermittent self-catheterisation
Authors: Martin Jennifer , Convie Liam , Mark David , McClure Mark
Published: February 2015

We report a strikingly unusual case of traumatic intraperitoneal perforation of an augmented bladder from clean intermittent self-catheterisation (CISC), which presented a unique diagnostic challenge. This case describes a 48-year-old T1 level paraplegic, who had undergone clamshell ileocystoplasty for detrusor overactivity, presenting with abdominal distension, vomiting and diarrhoea. Initial investigations were suggestive of disseminated peritoneal malignancy with ascitic fluid collections, but the ascitic fluid was found to be intraperitoneal urine from a perforation of the urinary bladder. This was associated with an inflammatory response in the surrounding structures causing an appearance of colonic thickening and omental disease. Although the diagnostic process was complex due to this patient’s medical history, the treatment plan initiated was non-operative, with insertion of an indwelling urinary catheter and radiologically guided drainage of pelvic and abdominal collections. Overdistension perforations of augmented urinary bladders have been reported, but few have described perforation from CISC.
Pneumatosis intestinalis an increasingly common radiological finding, benign or life-threatening? A case series
Authors: Blair Holly Alison , Baker Richard , Albazaz Raneem
Published: February 2015

This case series reviews two cases where elderly patients were found to have pneumatosis intestinalis on imaging. The two clinical presentations differed from one another, however, both were managed conservatively to good effect. In case one the patient presented with abdominal pain, a change in bowel habit and weight loss. In case two the patient presented with problematic diarrhoea, reduced oral intake, lethargy and weight loss. Both patients were haemodynamically stable and neither had an abnormal abdominal examination. Case 2 was started on oral metronidazole and by day 11 of treatment there was resolution of the pneumatosis on her abdominal X-ray and her diarrhoea had settled. These two cases illustrate the benefit of conservative management and avoidance of unnecessary surgical intervention in primary pneumatosis intestinalis. However, it is important to distinguish between these benign causes of pneumatosis intestinalis and those which are life-threatening in which surgery may be necessary.
A pain in the joints
Authors: Peters Rosie , Virani Farzana , Haddadin Yazan , Baldowska Helena
Published: February 2015

Arthralgia is a rare but recognised complication of meningococcal septicaemia. We report a case of a 29-year-old man presenting with a 24 h history of fever, joint swelling and subsequent development of a non-blanching, petechial rash. He was treated for probable meningococcal septicaemia and the causative pathogen was later identified asNeisseria meningitidis. He was treated with ceftriaxone and after 10 days the pain and swelling in his joints improved.
Eruptive furunculosis following the soak and smear regimen
Authors: Martires Kathryn , Sukhdeo Kumar , Meinhardt Eric
Published: February 2015

The ‘soak and smear’ regimen is a highly effective method for localised topical therapy employed by dermatologists for widespread inflammatory skin conditions. The regimen involves application of topical medication under occlusion after soaking in water. Complications from this treatment method are rare. We present a case of multiple, generalised methicillin-resistantStaphylococcus aureus(MRSA)-positive furuncles arising in a patient as an unexpected consequence of therapy. The case highlights an unanticipated risk of a commonly employed treatment amid an epidemic of MRSA in the community.
Colitis possibly induced by quetiapine
Authors: de Beaurepaire Renaud , Trinh Isabelle , Guirao Sophie , Taieb Muriel
Published: February 2015

A 39-year-old man with bipolar disorder was hospitalised for depression. He was started on quetiapine (titrated up to 300 mg), lactulose (a laxative) and tropatepine (an anticholinergic). Valpromide (a mood stabiliser) and prazepam were later added and rapidly withdrawn. Seven days after quetiapine initiation, the patient reported abdominal pain and constipation; 2 days later, CT revealed an important distention of the colon including the caecum and a pre-perforation. A subtotal colectomy was performed and histology confirmed necrotising ischaemic colitis. The patient survived. This is the first case reported so far of ischaemic colitis related to quetiapine, in the absence of other antipsychotics simultaneously prescribed. Tropatepine likely acted as a cofactor to determine colitis. Clinicians need to be aware of the potential danger of the co-prescription of quetiapine with tropatepine (and possibly other anticholinergics).
Spontaneous flexor tendon rupture in the palm
Authors: Patel Anant Piyush , Wong Kai Yuen
Published: February 2015

Spontaneous flexor intratendinous ruptures are rare and incompletely understood. They occur within the substance of the tendon, and in the absence of underlying pathological processes or direct trauma. We present an unusual case of spontaneous flexor digitorum profundus tendon rupture in the palm.
Correction of neglected vertical talus deformity in an adult
Authors: Lui Tun Hing
Published: February 2015

Congenital vertical talus is an uncommon foot deformity that is characterised by a fixed dorsal dislocation of the navicular on the talar head and neck. Left untreated, a congenital vertical talus causes significant long-term disability. We present a case of neglected vertical talus in a middle-aged woman who was successfully treated with resection of the talar head and tendon transfers.
Life-threatening haematuria caused by vancomycin-induced thrombocytopenia
Authors: Lobo Niyati , Ejiofor Kandi , Thurairaja Ramesh , Khan Muhammad Shamim
Published: February 2015

Thrombocytopenia is a rare side effect of vancomycin, an antibiotic that is often used to treat Gram-positive bacterial infections. A 67-year-old man developed bilateral pulmonary emboli and hospital-acquired pneumonia following left ureteric reimplantation. He was anticoagulated with rivaroxaban and started on intravenous vancomycin and gentamicin for treatment of pneumonia. After five doses of vancomycin, his platelet count dropped to a nadir of 0×109/L (baseline: 314×109/L) manifesting as visible heavy haematuria and haemodynamic instability due to excessive blood loss. Reversal of the thrombocytopenia was achieved with intravenous immunoglobulin, methylprednisolone and continuous platelet transfusions.
New diagnosis myasthenia gravis and preeclampsia in late pregnancy
Authors: Ozcan John , Balson Ian Frank , Dennis Alicia T
Published: February 2015

Myasthenia gravis is a chronic autoimmune disease of neuromuscular transmission resulting in fatigable skeletal muscle weakness. Preeclampsia is a multisystem disease of pregnancy which is characterised by hypertension and involvement of one or more organ systems. Both diseases are responsible for considerable morbidity and mortality for mother and fetus. The occurrence of both preeclampsia and myasthenia gravis in pregnancy is very rare, and conflicts arise when considering the optimal management of each disease.We present a case of a parturient who was newly diagnosed with both myasthenia gravis and preeclampsia in late pregnancy. Myasthenia treatment was started with prednisolone and pyridostigmine, and delivery was by caesarean section at 37 weeks gestation under spinal anaesthesia. Postnatally, the patient developed worsening of myasthenia and preeclampsia symptoms. We consider the anaesthetic implications for both diseases and describe our approach for the management of this case.
Sinonasal melanoma arising from conjunctival primary acquired melanosis
Authors: Shehata Mark , Gombos Dan , Bishop John , Zafereo Mark Edwin
Published: February 2015

A 66-year-old woman was treated with excision and cryotherapy for recurrent primary acquired melanosis (PAM) with atypia of the right conjunctiva. Four years later, she developed a melanoma of the ipsilateral inferior turbinate and nasolacrimal duct. She was treated with right medial maxillectomy and postoperative radiation therapy. This is the first reported case of conjunctival PAM resulting in delayed progression to melanoma in the nasolacrimal duct and sinonasal cavity.
First ever case of spontaneous triplet cornual pregnancy: management of laparoscopic cornual resection with modified endoloop method
Authors: Gosavi Arundhati , Lim Li Min , Agarwal Anupriya , Fong Yoke Fai
Published: February 2015

A 23-year-old woman, gravida 2 para 0, presented at 8 weeks gestation with a spontaneously conceived triplet cornual ectopic pregnancy. She was at high risk of ectopic pregnancy as she had been previously treated for pelvic inflammatory disease and had also undergone laparoscopic salpingostomy for right-sided ectopic pregnancy. She was clinically stable and her abdomen was soft and non-tender. The diagnosis was made on transvaginal ultrasound scan and this was confirmed on the three-dimensional scan. She was counselled about her treatment options and subsequently underwent laparoscopic cornual resection using the modified endoloop method. The estimated blood loss was 20 ml intraoperatively and the patient recovered well. She subsequently conceived spontaneously with an intrauterine pregnancy and underwent lower segment caesarean section at 37 weeks in view of previous laparoscopic cornual resection. Intraoperatively, the right cornua appeared normal and there was no sign of thinning.
Transient cardiogenic shock during a crisis of pheochromocytoma triggered by high-dose exogenous corticosteroids
Authors: Ibrahim Majd , Banga Sandeep , Venkatapuram Suneetha , Mungee Sudhir
Published: February 2015

We report a case of a 39-year-old woman who presented to the emergency department (ED) with symptoms of pharyngitis and fever. Diagnosed with streptococcal pharyngitis, she received antibiotics and dexamethasone, and was discharged. Within 24 h she returned to the ED with signs and symptoms of an acute coronary syndrome; she was thus given β-blockers. Her coronary angiogram was normal. She developed cardiogenic shock with an ejection fraction (EF) of 10% and apical ballooning on echocardiography. Her condition improved with optimal medical therapy. Subsequent testing weeks later confirmed the presence of a pheochromocytoma. Following prazosin and an adrenalectomy, all her antihypertensive medications were weaned and her EF normalised. We believe the high-dose exogenous corticosteroids triggered a pheochromocytoma crisis. The concomitant use of β-blockers without preceding α blockade resulted in cardiovascular collapse. Pheochromocytoma crisis must be included in the differential diagnosis of any dramatic haemodynamic collapse after administration of exogenous corticosteroid or β-blockers.
Sternoclavicular septic arthritis due to methicillin-resistantStaphylococcus aureusin a patient with a suprapubic catheter
Authors: Monteiro Nadine , Moleiro Filipa , Lérias Graça , Silva Alberto Mello
Published: February 2015

We report a case of a 74-year-old man who presented to the emergency department with a 1-week history of fever. He had a meatal stenosis and had a suprapubic catheter for 10 months, and had a recent hospitalisation for urosepsis with bacteraemia due to methicillin-resistantStaphylococcus aureusafter manipulation of the catheter. Clinical examinations were performed in the emergency department and the patient was hospitalised with the diagnosis of recurrent urinary tract infection. The following day, we noticed the development of a mass in the left sternoclavicular joint with inflammatory signs and excruciating pain. Ultrasonographic findings led to the diagnosis of left sternoclavicular synovitis, and methicillin-resistantS. aureusgrew in blood cultures leading to the diagnosis of sternoclavicular septic arthritis. Treatment with vancomycin and gentamicin was started and maintained for 4 weeks with complete resolution of symptoms and no complications or sequelae.
Implications of private sector Hib vaccine coverage for the introduction of public sector Hib-containing pentavalent vaccine in India: evidence from retrospective time series data
Authors: Sharma Abhishek , Kaplan Warren A , Chokshi Maulik , Hasan Farooqui Habib , Zodpey Sanjay P
Published: February 2015

Objective

Haemophilus influenzaetype b (Hib) vaccine has been available in India's private sector market since 1997. It was not until 14 December 2011 that the Government of India initiated the phased public sector introduction of a Hib (and DPT, diphtheria, pertussis, tetanus)-containing pentavalent vaccine. Our objective was to investigate the state-specific coverage and behaviour of Hib vaccine in India when it was available only in the private sector market but not in the public sector. This baseline information can act as a guide to determine how much coverage the public sector rollout of pentavalent vaccine (scheduled April 2015) will need to bear in order to achieve complete coverage.

Setting

16 of 29 states in India, 2009–2012.

Design

Retrospective descriptive secondary data analysis.

Data

(1) Annual sales of Hib vaccines, by volume, from private sector hospitals and retail pharmacies collected by IMS Health and (2) national household surveys.

Outcome measures

State-specific Hib vaccine coverage (%) and its associations with state-specific socioeconomic status.

Results

The overall private sector Hib vaccine coverage among the 2009–2012 birth cohort was low (4%) and varied widely among the studied Indian states (minimum 0.3%; maximum 4.6%). We found that private sector Hib vaccine coverage depends on urban areas with good access to the private sector, parent's purchasing capacity and private paediatricians’ prescribing practices. Per capita gross domestic product is a key explanatory variable. The annual Hib vaccine uptake and the 2009–2012 coverage levels were several times higher in the capital/metropolitan cities than the rest of the state, suggesting inequity in access to Hib vaccine delivered by the private sector.

Conclusions

If India has to achieve high and equitable Hib vaccine coverage levels, nationwide public sector introduction of the pentavalent vaccine is needed. However, the role of private sector in universal Hib vaccine coverage is undefined as yet but it should not be neglected as a useful complement to public sector services.
Prevalence of nosocomial pathogens in German ambulances: the SEKURE study
Authors: Wepler M , Stahl W , von Baum H , Wildermuth S , Dirks B , Georgieff M , Hafner S
Published: February 2015

Objective

The increasing prevalence of multidrug resistant bacteria is a problem in the inpatient care setting, and in the emergency care system. The aim of this observational, cross-sectional study was to evaluate the prevalence of pathogens on well-defined surfaces in German ambulances that have been designated as ‘ready for service’.

Methods

After informed consent was obtained, ambulance surfaces were sampled with agar plates for microbiological examination during an unannounced visit. A standardised questionnaire was used to obtain information regarding the disinfection protocols used at each rescue station.

Results

Methicillin resistant staphylococcus aureus contamination was present in 18 sampling surfaces from 11 out of 150 ambulance vehicles (7%) that were designated as ready for service. Contact surfaces directly surrounding patients or staff were most frequently contaminated with pathogens. However, bacterial contamination was not related to annual missions, methods or frequency of disinfection.

Conclusions

In accordance with previous studies, disinfection and cleaning of areas with direct contact to patients or staff seem to be the most challenging. This should also be reflected in disinfection guidelines and the related continuing education.
Modified technique for the subcutaneous implantation of radio transmitters in harbour seals (Phoca vitulina richardii) under field conditions
Authors: Manugian Suzanne , Van Bonn William , Harvey James T
Published: February 2015

A revised sedation and transmitter implantation technique was assessed for use in phocids under field conditions. Previous methods were modified with the intention of reducing animal handling time, complication rate, and logistic challenges associated with general anaesthesia and surgery. Pilot studies were conducted mimicking field conditions with close monitoring of animals (n=9) before implementing the procedure in the field on additional animals (n=32). No pilot study animals exhibited any complications. A number of animals were detected in the wild post release however tracking did not include follow‐up physical examination of all animals. One implanted animal presented to a rehabilitation facility and died under care and postmortem examination revealed death was not tag‐related. The combination of sedation and local anaesthesia enabled the successful expedited implantation of transmitters under field conditions. The authors conclude the method described is appropriate for field subcutaneous implantation surgeries on phocids.
Effect of feeding fermented rice punch on oestrous induction in anoestrous bitches
Authors: Choi Eul‐Soo , Yang Byoung‐Chul , Park Pu‐Rum , Chae Jung‐Il , Kim Dong‐Ku , Yoo Jae‐Kyu , Kim Dong‐Hoon , Cho Kyu‐Woan , Kong Il‐Keun
Published: February 2015

Introduction

As a consequence of poor productivity caused by a long anoestrous period, considerable research effort has been given to oestrus induction in dogs to enhance the productivity of young dogs and to preserve breeds.

Materials and methods

Oestrus was induced in 30 anoestrous bitches more than three months after the last oestrus. Bitches orally received fermented rice punch with or without bromocriptine once daily for 21 consecutive days. The bitches were divided into two groups (n=10 per group): Group (1) fed fermented rice punch and Group (2) administered bromocriptine (100 µg/kg/day) and fed fermented rice punch.

Results

The concentration of dopamine in fermented rice punch was 47.2 mg/kg (parts per million). Six of 10 (60.0 per cent) and seven of 10 (70.0 per cent) bitches showed pro‐oestrual bleeding in Groups 1 and 2, respectively. The mean and median values (min–max) to oestrus induction was not significantly different between Groups 1 and 2 (9.7±7.3, 6.5 (3–22) and 11.3±6.6, 7.9 (5–21) days) after treatment commencement (P>0.05). The pregnancy rate was very similar between Groups 1, 2 (66.0%) and control (66.0, 57.0 and 50.0 per cent). The mean and median values (min–max) of pups per bitch are also not significantly different between Groups 1, 2 and control (7.0±1.8, 7.0 (5–9) and 7.5±2.1, 7.5 (5–10) and 7.0±0, 7.0 (7–7)).

Conclusion

We suggest that rice punch effectively induces oestrus in bitches.
Mechanisms of renal hyporesponsiveness to BNP in heart failure
Authors: Egom Emmanuel E. , Feridooni Tiam , Hotchkiss Adam , Kruzliak Peter , Pasumarthi Kishore B.S.
Published: February 2015

The B-type natriuretic peptide (BNP), a member of the family of vasoactive peptides, is a potent natriuretic, diuretic, and vasodilatory peptide that contributes to blood pressure and volume homeostasis. These attributes make BNP an ideal drug that could aid in diuresing a fluid-overloaded patient who had poor or worsening renal function. Despite the potential benefits of BNP, accumulating evidence suggests that simply increasing the amount of circulating BNP does not necessarily increase natriuresis in patients with heart failure (HF). Moreover, despite high BNP levels, natriuresis falls when HF progresses from a compensated to a decompensated state, suggesting the emergence of renal resistance to BNP. Although likely multifactorial, several mechanisms have been proposed to explain renal hyporesponsiveness in HF, including, but not limited to, decreased renal BNP availability, down-regulation of natriuretic peptide receptors, and altered BNP intracellular signal transduction pathways. Thus, a better understanding of renal hyporesponsiveness in HF is required to devise strategies to develop novel agents and technologies that directly restore renal BNP efficiency. It is hoped that development of these new therapeutic approaches will serve to limit sodium retention in patients with HF, which may ultimately delay the progression to overt HF.
Changes in peptidergic fiber density in the synovium of mice with collagenase-induced acute arthritis
Authors: Murakami Kohei , Nakagawa Hiroshi , Nishimura Kazuhiko , Matsuo Saburo
Published: February 2015

The effect of acute osteoarthritis (OA) on peripheral nerve fibers (NFs) in synovial tissue, and their association with histological changes were investigated in collagenase-induced OA mice. Collagenase (10 U in 5 μL saline) was injected into the right knee, and the same volume of saline was injected into the left knee as the control. Mice were sacrificed 1, 2, 3, and 4 weeks after the collagenase injection. Histopathological changes in the knee joints were evaluated. The numbers of protein gene product (PGP) 9.5-, calcitonin-gene-related peptide (CGRP)-, and substance P (SP)-positive NFs in the synovial tissue were determined, and their densities in the tissue were calculated. The densities of PGP 9.5- and CGRP-positive NFs in the synovium were drastically decreased 1 week after the collagenase injection. However, by week 4, the density of PGP 9.5- and CGRP-positive NFs had recovered to 84% and 79% of their normal levels, respectively. Despite the poor correlation between the synovitis score and the density of CGRP- or SP-positive NFs in the synovium, the ossification rate of chondrophytes in chondro/osteophyte lesions correlated strongly with the density of CGRP-positive NFs (R = 0.855). These results suggest that the ossification of chondrophytes occurred in parallel with the increase in CGRP-positive fiber density in the synovium during the acute phase of collagenase-induced OA.
Arm Orthosis/Prosthesis Movement Control Based on Surface EMG Signal Extraction
Authors: Suberbiola Aaron , Zulueta Ekaitz , Lopez-Guede Jose Manuel , Etxeberria-Agiriano Ismael , Graña Manuel
Published: February 2015

This paper shows experimental results on electromyography (EMG)-based system control applied to motorized orthoses. Biceps and triceps EMG signals are captured through two biometrical sensors, which are then filtered and processed by an acquisition system. Finally an output/control signal is produced and sent to the actuators, which will then perform the actual movement, using algorithms based on autoregressive (AR) models and neural networks, among others. The research goal is to predict the desired movement of the lower arm through the analysis of EMG signals, so that the movement can be reproduced by an arm orthosis, powered by two linear actuators. In this experiment, best accuracy has achieved values up to 91%, using a fourth-order AR-model and 100ms block length.