Periventricular cyst as a complication of ventriculoperitoneal shunting in the context of intracranial haemorrhage: a case report and review of the literature.

Spontaneous intraventricular haemorrhage with hydrocephalus frequently requires neurosurgical intervention, including ventriculoperitoneal shunting. We describe a periventricular cyst following the placement of a ventriculoperitoneal shunt in a 67-year-old female patient. The patient was admitted for rehabilitation after a spontaneous left basal ganglia and diffuse intraventricular haemorrhage with hydrocephalus. Initial management included an extraventricular drain, followed by a ventriculoperitoneal shunt. On Day 5 of rehabilitation, the patient was urgently reviewed for reduced level of consciousness. A cerebrospinal fluid cyst was identified around the shunt catheter, with subacute haemorrhage within the cyst. The patient underwent a successful shunt revision, with rapid improvement in consciousness and resolution of the cyst. This case highlights the importance of pericatheter cyst as a differential diagnosis in patients with altered neurological status following ventriculoperitoneal shunting. Early detection and surgical revision can lead to rapid resolution of symptoms and a favourable prognosis.

Differentiating essential hypertension from autonomic dysreflexia: a case report.

INTRODUCTION: Autonomic dysreflexia (AD), a condition of critically raised blood pressure, is a severe complication of spinal cord injury. Primary (essential) hypertension may present with similar blood pressure levels to AD, though the causes, pathophysiology, presentation and treatment will differ. CASE PRESENTATION: We report a case of a 74-year-old patient with a C1 spinal injury, who developed primary (essential) hypertension during her rehabilitation phase of care, requiring extensive investigations for autonomic dysreflexia. Despite this, no underlying cause was found; essential hypertension was subsequently confirmed with 24-hour ambulatory blood pressure monitoring. Treatment with an ACE inhibitor was introduced to good effect. DISCUSSION: Essential hypertension can affect patients with spinal injury, even though most patients with higher level injuries (particularly cervical spinal cord injuries) are expected to have low resting baseline hypotension. Relevant features of this are presented within this case; a set of criteria to differentiate essential hypertension from autonomic dysreflexia are also proposed.

Tetraplegic spinal cord injury as a presentation of multiple myeloma: A case report.

Spinal cord injury is a devastating complication of cancers that exert physical compression on the spinal cord. Multiple myeloma is known predominantly as a condition that involves bony structures and can manifest with complications such as pathological fractures. However, involvement of other structures including spinal cord is a possible complication, with potentially catastrophic consequences. We describe a case of multiple myeloma presenting initially as severe paraplegia secondary to spinal cord compression in a 79-year-old man.

Recurrent syncope secondary to autonomic dysfunction in spinal cord injury: a case report.

High-level spinal cord injuries are often associated with autonomic impairment, which can result in orthostatic hypotension and syncope. Persistent autonomic dysfunction can manifest with disabling symptoms including recurrent syncopal events. We describe a case of autonomic failure resulting in recurrent syncopal events in a tetraplegic 66-year-old man.

Simultaneous Pulmonary Embolism and Carotid Thrombosis as a Presenting Manifestation of COVID-19.

Although COVID-19 was initially described predominantly as a respiratory infection, subsequent reports noted that it can produce generalised inflammation with effects on multiple organ systems. As a result, it is possible for patients with COVID-19, including those with severe disease, to present initially with nonrespiratory signs and symptoms. Neurological manifestations, including ischaemic stroke, may be the first presenting issue and can result from carotid thrombosis. Similarly, the risk of both arterial and venous thrombosis is increased in COVID-19, which may result from hypercoagulability associated with systemic inflammation.

Trends in osteoporosis diagnosis and management in Australia.

Trends in bone mineral density monitoring, and drug treatment for osteoporosis, in Australia were examined. Rates of DEXA scanning have increased in response to changes to government policy affecting reimbursement. The drug denosumab is being utilised at an increasing rate, while bisphosphonate use has declined. Osteoporosis prevalence remained stable over the same timeframe, while rate of hip fractures declined, suggesting that introduction of osteoporosis screening was associated with a reduction in adverse osteoporosis outcomes, but may also have been associated with overutilisation. INTRODUCTION: Radiology interventions to diagnose and medications to manage osteoporosis in Australia are reimbursed under the Medicare benefits schedule (MBS) and Pharmaceutical Benefits Scheme (PBS). Monitoring of these databases enables changes in utilisation of these practices to be monitored over time. METHODS: This study examined rates of utilisation for bone mineral density (BMD) measurement and osteoporosis pharmacotherapy subsidised under the MBS. Rates of osteoporosis and hip fracture were estimated using data reported by the Australian Bureau of Statistics (ABS) and Australian Institute for Health and Welfare (AIHW). RESULTS: Rates of BMD measurement increased since the technology was first reimbursed, with changes to policy regarding reimbursement for screening for individuals over 70 leading to an increase in BMD measurement after 2007. Prescribing rates also increased over time, initially with the introduction of oral bisphosphonates and subsequently for denosumab, which has subsequently become the most commonly prescribed agent for osteoporosis management in Australia, while bisphosphonate use has declined. Osteoporosis prevalence in Australia has remained relatively static at 3-4% of the population since 2001 to 2017, while rates of minimal trauma hip fracture hospitalisations have declined from 195 per 100,000 to 174 per 100,000 in the same timeframe. CONCLUSION: Available data indicates that osteoporosis screening rates changed over time from 2001 to 2018 and that changes to government policy had a significant effect on the rates at which screening was performed. Over the same timeframe, there was a sustained reduction in hip fracture hospitalisation rates, with no change to reported osteoporosis prevalence. This suggests that policy changes permitting unlimited access to BMD measurement were associated with a reduction in osteoporotic fractures, but may also have been associated with overutilisation. Prospective studies to assess the efficacy of specific policies to ensure screening is performed in accordance with best-practice guidelines may be desirable.

Trends in knee magnetic resonance imaging, arthroscopies and joint replacements in older Australians: still too much low-value care?

BACKGROUND: The objective of the study is to describe temporal trends and regional variations in the use of knee magnetic resonance imaging (MRI), knee arthroscopy and total knee replacement surgery in Australians older than 55 years. METHODS: Design: A retrospective descriptive study using routinely collected administrative data. MAIN OUTCOME MEASURES: Age-standardized rates of knee MRI, knee arthroscopy and knee replacement surgery from 2003 to 2017. RESULTS: Knee MRI rates increased from 216/100 000 in 2003, to 1509/100 000 in 2017 (sevenfold relative increase). Knee arthroscopy rates initially increased from 372/100 000 in 2003 to a maximum of 475/100 000 in 2011, before declining to 283/100 000 in 2017. Knee joint replacement surgery increased from 535/100 000 in 2003 to 840/100 000 in 2017 (57% relative increase). The use of MRI increased in all regions of Australia but to differing extents. Knee arthroscopy rates declined in all regions from 2011, but to differing extents. Knee joint replacement surgery increased at roughly the same rate across Australia. CONCLUSION: Knee arthroscopy rates increased before declining modestly in more recent years, most likely in response to evidence against its effectiveness. Knee MRI rates have continued to increase despite consistent recommendations against their routine use in the evaluation of knee pain. Future research could investigate potential drivers of the increased use of MRI, and of the continued use of arthroscopy. Further exploration of the extent to which either procedure explains the increase in numbers of knee joint replacements is also warranted.

Host specialisation and disparate evolution of Pyrenophora teres f. teres on barley and barley grass.

BACKGROUND: Pathogens evolve in an arms race, frequently evolving virulence that defeats resistance genes in their hosts. Infection of multiple hosts may accelerate this virulence evolution. Theory predicts that host diversity affects pathogen diversity, with more diverse hosts expected to harbour more diverse pathogens that reproduce sexually. We tested this hypothesis by comparing the microsatellite (SSR) genetic diversity of the barley leaf pathogen Pyrenophora teres f. teres (Ptt) from barley (monoculture) and barley grass (outbreeding). We also aim to investigate host specificity and attempt to track virulence on two barley cultivars, Maritime and Keel. RESULTS: Genetic diversity in barley Ptt populations was higher than in populations from barley grass. Barley Ptt populations also had higher linkage disequilibrium levels, indicating less frequent sexual reproduction, consistent with the Red Queen hypothesis theory that genetically diverse hosts should select for higher levels of sexual reproduction of the pathogen. SSR analyses indicate that host-associated Ptt populations do not share genotypes and have independent evolutionary histories. Pathogenicity studies showed host specificity as host-associated Ptt isolates could not cross-infect hosts. Minimum spanning network analyses indicated two major clusters of barley Ptt. One cluster represents Maritime virulent and isolates from Western Australia (WA). Low PhiPt population differentiation between WA populations and those from Maritime and Keel, indicated a WA origin of the Maritime and Keel virulences. The main minimum spanning network cluster is represented by a panmictic population structure, represented by isolates from all over Australia. CONCLUSIONS: Although barley Ptt populations are more diverse than barley grass Ptt populations, this may be a result of the size and number of founder Ptt populations to Australia, with larger and more barley Ptt populations introduced. More frequent sexual reproduction of Ptt on barley grass support the Red Queen Hypothesis and suggest evolutionary potential of pathogens on diverse hosts are high. Extensive gene flow of Ptt between regions in Australia is suggested to maintain a panmictic population structure, with human-mediated dispersal aiding in virulence evolution of Ptt on barley.

Dental appliance therapy in pantothenate kinase-associated neurodegeneration: Case report.

Pantothenate kinase-associated neurodegeneration (PKAN) is a rare condition associated with severe protrusive lingual dystonia, a form of oromandibular dystonia. Dental appliance therapy has been described for oromandibular dystonia however there is a lack of literature regarding its application specifically to PKAN. In this report, the authors describe the use of an appliance in conjunction with botulinum toxin injections for the symptomatic treatment of this condition. A satisfactory outcome is achieved which suggests this technique may be of use to other clinicians.

Discovery of a Parenteral Small Molecule Coagulation Factor XIa Inhibitor Clinical Candidate (BMS-962212).

Factor XIa (FXIa) is a blood coagulation enzyme that is involved in the amplification of thrombin generation. Mounting evidence suggests that direct inhibition of FXIa can block pathologic thrombus formation while preserving normal hemostasis. Preclinical studies using a variety of approaches to reduce FXIa activity, including direct inhibitors of FXIa, have demonstrated good antithrombotic efficacy without increasing bleeding. On the basis of this potential, we targeted our efforts at identifying potent inhibitors of FXIa with a focus on discovering an acute antithrombotic agent for use in a hospital setting. Herein we describe the discovery of a potent FXIa clinical candidate, 55 (FXIa Ki = 0.7 nM), with excellent preclinical efficacy in thrombosis models and aqueous solubility suitable for intravenous administration. BMS-962212 is a reversible, direct, and highly selective small molecule inhibitor of FXIa.

New species of Tulasnella associated with terrestrial orchids in Australia.

Recent studies using sequence data from eight sequence loci and coalescent-based species delimitation methods have revealed several species-level lineages of Tulasnella associated with the orchid genera Arthrochilus, Caleana, Chiloglottis, and Drakaea in Australia. Here we formally describe three of those species, Tulasnella prima, T. secunda, and T. warcupii spp. nov., as well as an additional Tulasnella species associated with Chiloglottis growing in Sphagnum, T. sphagneti sp. nov. Species were identified by phylogenetic analyses of the ITS with up to 1.3 % sequence divergence within taxa and a minimum of 7.6 % intraspecific divergence. These new Tulasnella (Tulasnellaceae, Cantharellales) species are currently only known from orchid hosts, with each fungal species showing a strong relationship with an orchid genus. In this study, T. prima and T. sphagneti associate with Chiloglottis, while T. secunda associates with Drakaea and Caleana, and T. warcupii associates with Arthrochilus oreophilus.

Practical time considerations for optically stimulated luminescent dosimetry (OSLD) in total body irradiation.

Total body irradiation (TBI) treatments are used to treat the whole body in preparation for hematopoietic stem cell (or bone marrow) transplantation. Our standard clinical regimen is a 12 Gy in 6 fraction, bi-daily technique using 6 MV X-rays at an extended Source-to-Surface distance (SSD) of 300 cm. Utilizing these characteristics, the beam dose rate is reduced below 7 cGy/min as is standard for TBI treatment. Dose received by the patient is monitored using optically stimulated luminescent dosimetry (OSLD). This work presents some practical calibration corrections based on time-dependant factors for OSLD calibration related to TBI procedure. Results have shown that a negligible difference is seen in OSL sensitivity for 6 MV X-rays irradiated in standard SSD (100 cm) and high dose rate (600 cGy/min) conditions compared to extended SSD (300 cm) and low TBI dose rate (6 cGy/min) conditions. Results have also shown that whilst short term signal fading occurs in the OSL after irradiation at a high dose rate (37% reduction in signal in the first 15 min), thereafter, negligible differences are seen in the OSL signal between 600 and 7 cGy/min irradiations. Thus a direct comparison can be made between calibration OSLs and clinical TBI OSLs between 15 min and 2 h. Finally a table is presented to provide corrections between calibration OSL readout and clinical TBI dose readout for a period up to 7 days. Combining these three results allows users to pre-irradiate their calibration OSLs at standard dose rate and SSD, up to 1 week prior to clinical treatment, and still provide accurate in-vivo dosimetry. This can help with time saving and work efficiency in the clinic.

Weeds, as ancillary hosts, pose disproportionate risk for virulent pathogen transfer to crops.

BACKGROUND: The outcome of the arms race between hosts and pathogens depends heavily on the interactions between their genetic diversity, population size and transmission ability. Theory predicts that genetically diverse hosts will select for higher virulence and more diverse pathogens than hosts with low genetic diversity. Cultivated hosts typically have lower genetic diversity and thus small effective population sizes, but can potentially harbour large pathogen population sizes. On the other hand, hosts, such as weeds, which are genetically more diverse and thus have larger effective population sizes, usually harbour smaller pathogen population sizes. Large pathogen population sizes may lead to more opportunities for mutation and hence more diverse pathogens. Here we test the predictions that pathogen neutral genetic diversity will increase with large pathogen population sizes and host diversity, whereas diversity under selection will increase with host diversity. We assessed and compared the diversity of a fungal pathogen, Rhynchosporium commune, on weedy barley grass (which have a large effective population size) and cultivated barley (low genetic diversity) using microsatellites, effector locus nip1 diversity and pathogen aggressiveness in order to assess the importance of weeds in the evolution of the neutral and selected diversity of pathogens. RESULTS: The findings indicated that the large barley acreage and low host diversity maintains higher pathogen neutral genetic diversity and lower linkage disequilibrium, while the weed maintains more pathotypes and higher virulence diversity at nip1. Strong evidence for more pathogen migration from barley grass to barley suggests transmission of virulence from barley grass to barley is common. CONCLUSIONS: Pathogen census population size is a better predictor for neutral genetic diversity than host diversity. Despite maintaining a smaller pathogen census population size, barley grass acts as an important ancillary host to R. commune, harbouring highly virulent pathogen types capable of transmission to barley. Management of disease on crops must therefore include management of weedy ancillary hosts, which may harbour disproportionate supplies of virulent pathogen strains.

Novel phenylalanine derived diamides as Factor XIa inhibitors.

The synthesis, structural activity relationships (SAR), and selectivity profile of a potent series of phenylalanine diamide FXIa inhibitors will be discussed. Exploration of P1 prime and P2 prime groups led to the discovery of compounds with high FXIa affinity, good potency in our clotting assay (aPPT), and high selectivity against a panel of relevant serine proteases as exemplified by compound 21. Compound 21 demonstrated good in vivo efficacy (EC50=2.8µM) in the rabbit electrically induced carotid arterial thrombosis model (ECAT).

Radiation dose measurements of an on-board imager X-ray unit using optically-stimulated luminescence dosimeters.

Cone beam computed tomography (CBCT) is now widely used to image radiotherapy patients prior to treatment for the purpose of accurate patient setup. However each CBCT image delivered to a patient increases the total radiation dose that they receive. The measurement of the dose delivered from the CBCT images is not readily performed in the clinic. In this study, we have used commercially available optically stimulated luminescence (OSLD) dosimeters to measure the dose delivered by the Varian OBI on a radiotherapy linear accelerator. Calibration of the OSLDs was achieved by using a therapeutic X-ray unit. The dose delivered by a head CBCT scan was found to be 3.2 ± 0.3 mGy which is similar in magnitude to the dose of a head computed tomography (CT) scan. The results of this study suggest that the radiation hazard associated with CBCT is of a similar nature to that of conventional CT scans. We have also demonstrated that the OSLDs are suitable for these low X-ray dose measurements.

Structure-based design of inhibitors of coagulation factor XIa with novel P1 moieties.

Compound 2 was previously identified as a potent inhibitor of factor XIa lacking oral bioavailability. A structure-based approach was used to design analogs of 2 with novel P1 moieties with good selectivity profiles and oral bioavailability. Further optimization of the P1 group led to the identification of a 4-chlorophenyltetrazole P1 analog, which when combined with further modifications to the linker and P2' group provided compound 32 with FXIa Ki=6.7 nM and modest oral exposure in dogs.

Phylogenetic and microsatellite markers for Tulasnella (Tulasnellaceae) mycorrhizal fungi associated with Australian orchids.

PREMISE OF THE STUDY: Phylogenetic and microsatellite markers were developed for Tulasnella mycorrhizal fungi to investigate fungal species identity and diversity. These markers will be useful in future studies investigating the phylogenetic relationship of the fungal symbionts, specificity of orchid-mycorrhizal associations, and the role of mycorrhizae in orchid speciation within several orchid genera. • METHODS AND RESULTS: We generated partial genome sequences of two Tulasnella symbionts originating from Chiloglottis and Drakaea orchid species with 454 genome sequencing. Cross-genus transferability across mycorrhizal symbionts associated with multiple genera of Australian orchids (Arthrochilus, Chiloglottis, Drakaea, and Paracaleana) was found for seven phylogenetic loci. Five loci showed cross-transferability to Tulasnella from other orchid genera, and two to Sebacina. Furthermore, 11 polymorphic microsatellite loci were developed for Tulasnella from Chiloglottis. • CONCLUSIONS: Highly informative markers were obtained, allowing investigation of mycorrhizal diversity of Tulasnellaceae associated with a wide variety of terrestrial orchids in Australia and potentially worldwide.

Permanent genetic resources added to Molecular Ecology Resources Database 1 February 2011-31 March 2011.

This article documents the addition of 111 microsatellite marker loci to the Molecular Ecology Resources Database. Loci were developed for the following species: Acipenser oxyrinchus desotoi, Anopheles nuneztovari sensu lato, Asellus aquaticus, Calopteryx splendens, Calopteryx virgo, Centaurea aspera, Centaurea seridis, Chilina dombeyana, Proctoeces cf. lintoni and Pyrenophora teres f. teres.

Mycoplasma pneumonia and its complications.

Mycoplasma pneumoniae continues to be the most frequent cause of atypical pneumonia. Fortunately, the antibiotics listed in this article are generally very effective. Major skills are needed to detect M pneumoniae extrapulmonary diseases, which require a special heightened awareness and sensitivity. It is not known whether early therapy prevents dreaded complications.