Visual stimulation induces distinct forms of sensitization of On-Off direction-selective ganglion cell responses in the dorsal and ventral retina.

Experience-dependent modulation of neuronal responses is a key attribute in sensory processing. In the mammalian retina, the On-Off direction-selective ganglion cell (On-Off DSGC) is well known for its robust direction selectivity. However, how the On-Off DSGC light responsiveness dynamically adjusts to the changing visual environment is underexplored. Here, we report that On-Off DSGCs tuned to posterior motion direction (pDSGCs) in mice of both sexes can be transiently sensitized by prior stimuli. Notably, distinct sensitization patterns are found in dorsal and ventral pDSGCs. Although responses of both dorsal and ventral pDSGCs to dark stimuli (Off responses) are sensitized, only dorsal cells show sensitization of responses to bright stimuli (On responses). Visual stimulation to the dorsal retina potentiates a sustained excitatory input from Off bipolar cells, leading to tonic depolarization of pDSGCs. Such tonic depolarization propagates from the Off to the On dendritic arbor of the pDSGC to sensitize its On response. We also identified a previously overlooked feature of DSGC dendritic architecture that can support dendritic integration between On and Off dendritic layers bypassing the soma. By contrast, ventral pDSGCs lack a sensitized tonic depolarization and thus do not exhibit sensitization of their On responses. Our results highlight a topographic difference in Off bipolar cell inputs underlying divergent sensitization patterns of dorsal and ventral pDSGCs. Moreover, substantial crossovers between dendritic layers of On-Off DSGCs suggest an interactive dendritic algorithm for processing On and Off signals before they reach the soma.Significance StatementVisual neuronal responses are dynamically influenced by the prior visual experience. This form of plasticity reflects the efficient coding of the naturalistic environment by the visual system. We found that a class of retinal output neurons, On-Off direction-selective ganglion cells, transiently increase their responsiveness after visual stimulation. Cells located in dorsal and ventral retina exhibit distinct sensitization patterns due to different adaptive properties of Off bipolar cell signaling. A previously overlooked dendritic morphological feature of the On-Off direction-selective ganglion cell is implicated in the crosstalk between On and Off pathways during sensitization. Together, these findings uncover a topographic difference in the adaptive encoding of upper and lower visual fields and the underlying neural mechanism in the dorsal and ventral retina.

Two mechanisms for direction selectivity in a model of the primate starburst amacrine cell.

In a recent study, visual signals were recorded for the first time in starburst amacrine cells of the macaque retina, and, as for mouse and rabbit, a directional bias observed in calcium signals was recorded from near the dendritic tips. Stimulus motion from the soma toward the tip generated a larger calcium signal than motion from the tip toward the soma. Two mechanisms affecting the spatiotemporal summation of excitatory postsynaptic currents have been proposed to contribute to directional signaling at the dendritic tips of starbursts: (1) a "morphological" mechanism in which electrotonic propagation of excitatory synaptic currents along a dendrite sums bipolar cell inputs at the dendritic tip preferentially for stimulus motion in the centrifugal direction; (2) a "space-time" mechanism that relies on differences in the time-courses of proximal and distal bipolar cell inputs to favor centrifugal stimulus motion. To explore the contributions of these two mechanisms in the primate, we developed a realistic computational model based on connectomic reconstruction of a macaque starburst cell and the distribution of its synaptic inputs from sustained and transient bipolar cell types. Our model suggests that both mechanisms can initiate direction selectivity in starburst dendrites, but their contributions differ depending on the spatiotemporal properties of the stimulus. Specifically, the morphological mechanism dominates when small visual objects are moving at high velocities, and the space-time mechanism contributes most for large visual objects moving at low velocities.

Species-specific wiring for direction selectivity in the mammalian retina.

Directionally tuned signalling in starburst amacrine cell (SAC) dendrites lies at the heart of the circuit that detects the direction of moving stimuli in the mammalian retina. The relative contributions of intrinsic cellular properties and network connectivity to SAC direction selectivity remain unclear. Here we present a detailed connectomic reconstruction of SAC circuitry in mouse retina and describe two previously unknown features of synapse distributions along SAC dendrites: input and output synapses are segregated, with inputs restricted to proximal dendrites; and the distribution of inhibitory inputs is fundamentally different from that observed in rabbit retina. An anatomically constrained SAC network model suggests that SAC­SAC wiring differences between mouse and rabbit retina underlie distinct contributions of synaptic inhibition to velocity and contrast tuning and receptive field structure. In particular, the model indicates that mouse connectivity enables SACs to encode lower linear velocities that account for smaller eye diameter, thereby conserving angular velocity tuning. These predictions are confirmed with calcium imaging of mouse SAC dendrites responding to directional stimuli.

Light-evoked glutamate transporter EAAT5 activation coordinates with conventional feedback inhibition to control rod bipolar cell output.

In the retina, modulation of the amplitude of dim visual signals primarily occurs at axon terminals of rod bipolar cells (RBCs). GABA and glycine inhibitory neurotransmitter receptors and the excitatory amino acid transporter 5 (EAAT5) modulate the RBC output. EAATs clear glutamate from the synapse, but they also have a glutamate-gated chloride conductance. EAAT5 acts primarily as an inhibitory glutamate-gated chloride channel. The relative role of visually evoked EAAT5 inhibition compared with GABA and glycine inhibition has not been addressed. In this study, we determine the contribution of EAAT5-mediated inhibition onto RBCs in response to light stimuli in mouse retinal slices. We find differences and similarities in the two forms of inhibition. Our results show that GABA and glycine mediate nearly all lateral inhibition onto RBCs, as EAAT5 is solely a mediator of RBC feedback inhibition. We also find that EAAT5 and conventional GABA inhibition both contribute to feedback inhibition at all stimulus intensities. Finally, our in silico modeling compares and contrasts EAAT5-mediated to GABA- and glycine-mediated feedback inhibition. Both forms of inhibition have a substantial impact on synaptic transmission to the postsynaptic AII amacrine cell. Our results suggest that the late phase EAAT5 inhibition acts with the early phase conventional, reciprocal GABA inhibition to modulate the rod signaling pathway between rod bipolar cells and their downstream synaptic targets.NEW & NOTEWORTHY Excitatory amino acid transporter 5 (EAAT5) glutamate transporters have a chloride channel that is strongly activated by glutamate, which modulates excitatory signaling. We found that EAAT5 is a major contributor to feedback inhibition on rod bipolar cells. Inhibition to rod bipolar cells is also mediated by GABA and glycine. GABA and glycine mediate the early phase of feedback inhibition, and EAAT5 mediates a more delayed inhibition. Together, inhibitory transmitters and EAAT5 coordinate to mediate feedback inhibition, controlling neuronal output.

A novel mechanism of cone photoreceptor adaptation.

An animal's ability to survive depends on its sensory systems being able to adapt to a wide range of environmental conditions, by maximizing the information extracted and reducing the noise transmitted. The visual system does this by adapting to luminance and contrast. While luminance adaptation can begin at the retinal photoreceptors, contrast adaptation has been shown to start at later stages in the retina. Photoreceptors adapt to changes in luminance over multiple time scales ranging from tens of milliseconds to minutes, with the adaptive changes arising from processes within the phototransduction cascade. Here we show a new form of adaptation in cones that is independent of the phototransduction process. Rather, it is mediated by voltage-gated ion channels in the cone membrane and acts by changing the frequency response of cones such that their responses speed up as the membrane potential modulation depth increases and slow down as the membrane potential modulation depth decreases. This mechanism is effectively activated by high-contrast stimuli dominated by low frequencies such as natural stimuli. However, the more generally used Gaussian white noise stimuli were not effective since they did not modulate the cone membrane potential to the same extent. This new adaptive process had a time constant of less than a second. A critical component of the underlying mechanism is the hyperpolarization-activated current, Ih, as pharmacologically blocking it prevented the long- and mid- wavelength sensitive cone photoreceptors (L- and M-cones) from adapting. Consistent with this, short- wavelength sensitive cone photoreceptors (S-cones) did not show the adaptive response, and we found they also lacked a prominent Ih. The adaptive filtering mechanism identified here improves the information flow by removing higher-frequency noise during lower signal-to-noise ratio conditions, as occurs when contrast levels are low. Although this new adaptive mechanism can be driven by contrast, it is not a contrast adaptation mechanism in its strictest sense, as will be argued in the Discussion.

Impact of light-adaptive mechanisms on mammalian retinal visual encoding at high light levels.

A persistent change in illumination causes light-adaptive changes in retinal neurons. Light adaptation improves visual encoding by preventing saturation and by adjusting spatiotemporal integration to increase the signal-to-noise ratio (SNR) and utilize signaling bandwidth efficiently. In dim light, the visual input contains a greater relative amount of quantal noise, and vertebrate receptive fields are extended in space and time to increase SNR. Whereas in bright light, SNR of the visual input is high, the rate of synaptic vesicle release from the photoreceptors is low so that quantal noise in synaptic output may limit SNR postsynaptically. Whether and how reduced synaptic SNR impacts spatiotemporal integration in postsynaptic neurons remains unclear. To address this, we measured spatiotemporal integration in retinal horizontal cells and ganglion cells in the guinea pig retina across a broad illumination range, from low to high photopic levels. In both cell types, the extent of spatial and temporal integration changed according to an inverted U-shaped function consistent with adaptation to low SNR at both low and high light levels. We show how a simple mechanistic model with interacting, opponent filters can generate the observed changes in ganglion cell spatiotemporal receptive fields across light-adaptive states and postulate that retinal neurons postsynaptic to the cones in bright light adopt low-pass spatiotemporal response characteristics to improve visual encoding under conditions of low synaptic SNR.

Assembly: a resource for assembled genomes at NCBI.

The NCBI Assembly database (www.ncbi.nlm.nih.gov/assembly/) provides stable accessioning and data tracking for genome assembly data. The model underlying the database can accommodate a range of assembly structures, including sets of unordered contig or scaffold sequences, bacterial genomes consisting of a single complete chromosome, or complex structures such as a human genome with modeled allelic variation. The database provides an assembly accession and version to unambiguously identify the set of sequences that make up a particular version of an assembly, and tracks changes to updated genome assemblies. The Assembly database reports metadata such as assembly names, simple statistical reports of the assembly (number of contigs and scaffolds, contiguity metrics such as contig N50, total sequence length and total gap length) as well as the assembly update history. The Assembly database also tracks the relationship between an assembly submitted to the International Nucleotide Sequence Database Consortium (INSDC) and the assembly represented in the NCBI RefSeq project. Users can find assemblies of interest by querying the Assembly Resource directly or by browsing available assemblies for a particular organism. Links in the Assembly Resource allow users to easily download sequence and annotations for current versions of genome assemblies from the NCBI genomes FTP site.

Time course of EPSCs in ON-type starburst amacrine cells is independent of dendritic location.

KEY POINTS: Direction selectivity has been widely studied as an example of a complex neural computation. Directional GABA release from starburst amacrine cells (SBACs) is critical for generating directional signals in direction-selective ganglion cells. The mechanisms producing the directional release remain unclear. For SBACs, ordered distribution of sustained and transient bipolar cell inputs along the dendrites is proposed to generate directional GABA release. This study tests whether this hypothesis applies to ON-type SBACs. EPSCs activated at proximal and distal dendritic locations have the same time course. Therefore, the ordered arrangement of inputs from bipolar cells with different kinetic properties cannot be responsible for generating directional GABA release from ON-type SBACs. ABSTRACT: Direction selectivity in the retina relies critically on directionally asymmetric GABA release from the dendritic tips of starburst amacrine cells (SBACs). GABA release from each radially directed dendrite is larger for motion outward from the soma toward the dendritic tips than for motion inwards toward the soma. The biophysical mechanisms generating these directional signals remain controversial. A model based on electron-microscopic reconstructions of the mouse retina proposed that an ordered arrangement of kinetically distinct bipolar cell inputs to ON- and OFF-type SBACs could produce directional GABA release. We tested this prediction by measuring the time course of EPSCs in ON-type SBACs in the mouse retina, activated by proximal and distal light stimulation. Contrary to the prediction, the kinetics of the excitatory inputs were independent of dendritic location. Computer simulations based on 3D reconstructions of SBAC dendrites demonstrated that the response kinetics of distal inputs were not significantly altered by dendritic filtering. These direct physiological measurements, do not support the hypothesis that directional signals in SBACs arise from the ordered arrangement of kinetically distinct bipolar cell inputs.

Alternating ptosis associated with asialo-GM1 and GD1b antibodies.

Miller Fisher syndrome (MFS), variant of acute inflammatory demyelinating polyradiculoneuropathy, is recognized as clinical triad (ophthalmoplegia-ataxia-areflexia). Ganglioside antibodies play an important role in the pathogenesis of acute polyradiculoneuropathy including MFS. To our knowledge, there has been no report of MFS presenting with atypical alternating ptosis or with concurrent elevation of serum GD1 and asialo-GM1 antibody titers, and negative titers of GQ1b antibody such as our patient. Our objective is to report MFS with unusual symptoms and to share our diagnostic approach. We report a rare case of MFS presenting with alternating eyelid ptosis, paresthesia, and ataxia after a respiratory infection. Initial neurological examination revealed left eyelid ptosis, hyporeflexia, positive Romberg sign, and ataxia. The ice pack test was negative. Three days later, contralateral ptosis was observed, associated with areflexia and worsened ataxia. However, there was significant improvement of the previous left eyelid ptosis. Serology revealed elevated asialo-GM1 and GD1b antibodies. Acetylcholine receptor antibodies were negative. Cerebral spinal fluid revealed elevated IgG index. Nerve conduction studies (NCS) performed four days after the onset of symptoms showed normal nerve conduction velocities and F-waves, and absent bilateral H-reflexes. Repetitive nerve stimulation (3 Hz) showed no decrement of compound muscle action potentials. Trial with a single dose of pyridostigmine showed no clinical improvement. The symptoms resolved without intervention. NCS 18 days after onset of symptoms showed mildly prolonged F-waves and absent H-reflexes. This case highlights an atypical presentation of MFS and raises the awareness of a rare autoantibody associated with it.

Inhibitory input to the direction-selective ganglion cell is saturated at low contrast.

Direction-selective ganglion cells (DSGCs) respond selectively to motion toward a "preferred" direction, but much less to motion toward the opposite "null" direction. Directional signals in the DSGC depend on GABAergic inhibition and are observed over a wide range of speeds, which precludes motion detection based on a fixed temporal correlation. A voltage-clamp analysis, using narrow bar stimuli similar in width to the receptive field center, demonstrated that inhibition to DSGCs saturates rapidly above a threshold contrast. However, for wide bar stimuli that activate both the center and surround, inhibition depends more linearly on contrast. Excitation for both wide and narrow bars was also more linear. We propose that positive feedback, likely within the starburst amacrine cell or its network, produces steep saturation of inhibition at relatively low contrast. This mechanism renders GABA release essentially contrast and speed invariant, which enhances directional signals for small objects and thereby increases the signal-to-noise ratio for direction-selective signals in the spike train over a wide range of stimulus conditions. The steep saturation of inhibition confers to a neuron immunity to noise in its spike train, because when inhibition is strong no spikes are initiated.

NaV1.1 channels in axon initial segments of bipolar cells augment input to magnocellular visual pathways in the primate retina.

In the primate visual system, the ganglion cells of the magnocellular pathway underlie motion and flicker detection and are relatively transient, while the more sustained ganglion cells of the parvocellular pathway have comparatively lower temporal resolution, but encode higher spatial frequencies. Although it is presumed that functional differences in bipolar cells contribute to the tuning of the two pathways, the properties of the relevant bipolar cells have not yet been examined in detail. Here, by making patch-clamp recordings in acute slices of macaque retina, we show that the bipolar cells within the magnocellular pathway, but not the parvocellular pathway, exhibit voltage-gated sodium (NaV), T-type calcium (CaV), and hyperpolarization-activated, cyclic nucleotide-gated (HCN) currents, and can generate action potentials. Using immunohistochemistry in macaque and human retinae, we show that NaV1.1 is concentrated in an axon initial segment (AIS)-like region of magnocellular pathway bipolar cells, a specialization not seen in transient bipolar cells of other vertebrates. In contrast, CaV3.1 channels were localized to the somatodendritic compartment and proximal axon, but were excluded from the AIS, while HCN1 channels were concentrated in the axon terminal boutons. Simulations using a compartmental model reproduced physiological results and indicate that magnocellular pathway bipolar cells initiate spikes in the AIS. Finally, we demonstrate that NaV channels in bipolar cells augment excitatory input to parasol ganglion cells of the magnocellular pathway. Overall, the results demonstrate that selective expression of voltage-gated channels contributes to the establishment of parallel processing in the major visual pathways of the primate retina.

Cones respond to light in the absence of transducin ß subunit.

Mammalian cones respond to light by closing a cGMP-gated channel via a cascade that includes a heterotrimeric G-protein, cone transducin, comprising Gαt2, Gß3 and Gγt2 subunits. The function of Gßγ in this cascade has not been examined. Here, we investigate the role of Gß3 by assessing cone structure and function in Gß3-null mouse (Gnb3(-/-)). We found that Gß3 is required for the normal expression of its partners, because in the Gnb3(-/-) cone outer segments, the levels of Gαt2 and Gγt2 are reduced by fourfold to sixfold, whereas other components of the cascade remain unaltered. Surprisingly, Gnb3(-/-) cones produce stable responses with normal kinetics and saturating response amplitudes similar to that of the wild-type, suggesting that cone phototransduction can function efficiently without a Gß subunit. However, light sensitivity was reduced by approximately fourfold in the knock-out cones. Because the reduction in sensitivity was similar in magnitude to the reduction in Gαt2 level in the cone outer segment, we conclude that activation of Gαt2 in Gnb3(-/-) cones proceeds at a rate approximately proportional to its outer segment concentration, and that activation of phosphodiesterase and downstream cascade components is normal. These results suggest that the main role of Gß3 in cones is to establish optimal levels of transducin heteromer in the outer segment, thereby indirectly contributing to robust response properties.

Directional summation in non-direction selective retinal ganglion cells.

Retinal ganglion cells receive inputs from multiple bipolar cells which must be integrated before a decision to fire is made. Theoretical studies have provided clues about how this integration is accomplished but have not directly determined the rules regulating summation of closely timed inputs along single or multiple dendrites. Here we have examined dendritic summation of multiple inputs along On ganglion cell dendrites in whole mount rat retina. We activated inputs at targeted locations by uncaging glutamate sequentially to generate apparent motion along On ganglion cell dendrites in whole mount retina. Summation was directional and dependent13 on input sequence. Input moving away from the soma (centrifugal) resulted in supralinear summation, while activation sequences moving toward the soma (centripetal) were linear. Enhanced summation for centrifugal activation was robust as it was also observed in cultured retinal ganglion cells. This directional summation was dependent on hyperpolarization activated cyclic nucleotide-gated (HCN) channels as blockade with ZD7288 eliminated directionality. A computational model confirms that activation of HCN channels can override a preference for centripetal summation expected from cell anatomy. This type of direction selectivity could play a role in coding movement similar to the axial selectivity seen in locust ganglion cells which detect looming stimuli. More generally, these results suggest that non-directional retinal ganglion cells can discriminate between input sequences independent of the retina network.

Neuromyelitis optica in patients with coexisting human immunodeficiency virus infections.

Two patients with known human immunodeficiency virus (HIV) infections and receiving antiretroviral treatment developed neuromyelitis optica (Devic's disease). One patient tested positive for serum aquaporin-4 immunoglobulin G antibodies. Both patients were treated with high dose pulsed intravenous methylprednisolone followed by standard sessions of plasma exchange both at the onset attack and during disease relapses. For maintenance therapy, one patient received rituximab infusions and the second patient received mycophenolate mofetil orally. Despite treatment, both patients are currently wheelchair-bound due to severe paraparesis. Neuromyelitis optica can occur in the course of HIV infection and poses an ongoing therapeutic challenge.

Risk Management and Mitigating Risk Opportunities for Opioid Prescribing.

All clinicians are ethically obliged to prescribe responsibly and cautiously to diminish the potential for opioid diversion and to help minimize the growth of the current opioid abuse epidemic. Podiatric physicians should establish procedures to better control and limit opioid prescription and develop analgesic regimens to treat pain. The main purpose and goal of this review is to present data congruent with clinical, medical, and legal reports for allowing an appreciation of the possibility of the risk assumed when ordering and prescribing opioids within the podiatric medical profession. First, the concept and process of risk management, illustrated using a root cause analysis approach, is introduced, and application of these principles specifically to opioid prescribing is presented. Then, several examples found in both the medical and legal literature documenting the reasons for opioid prescription risk are presented. Finally, mitigating strategies for safe opioid prescribing are offered so that mitigation of opioid harm can be possible and realized by the lower-extremity specialist. Risk management strategies and tools to mitigate opioid harm, lessen opioid adverse effects, and reduce opioid deaths are presented narratively and graphically.

An Appraisal of Opioid Treatment Agreements for the Podiatric Physician.

Opioid treatment agreements are written agreements between physicians and patients that represent strategies enumerating the risks associated with opioid medications. These opioid treatment agreements set expectations and obligations, as well as identify responsibilities for both patient and prescriber for opioid therapy. Some critics assert that these agreements are cumbersome and degrade the patient once they enter into these agreements. A systemic literature search and review using the Preferred Reporting Item for Systematic Reviews and Meta-Analyses (PRISMA) tool was used to find citations describing opioid treatment agreements and their use. Then eligible and appropriate citations were dissected and analyzed. Using the available federal and state opioid prescribing policies, best practice guidelines as well as positive aspects of reviewed literature citations and avoiding bias, degrading, or macroaggression language, a non-cumbersome opioid treatment agreement specific to podiatric medicine was created. A balance argument for the use of opioid treatment agreements to avoid opioid use disorder that is grounded in clinical literature and commentaries are presented. A one-page sensible opioid treatment agreement specific to podiatric medicine, which is similar to more complex cumbersome ones that are found in the literature, and that may be used as part of any podiatric procedural or surgical inform consent, was created and is presented for review. The perception of defending opioid treatment agreements as documents of disclosure to assist patients in their autonomy was offered. Building on the systemic review findings and concept of using elements of disclosure, a model for an analgesic treatment as a one-page informational document to enhance podiatric physicians to create a specific individual analgesic treatment agreement mirroring the scope of podiatric practices that can be incorporated into procedural and surgical inform consent documents was offered.

An Appraisal of Using Opioids in Patients with Opioid Use Disorder.

Podiatric physicians have come to realize that opioid use disorder (OUD) is a public health crisis causing morbidity, mortality, lost productivity, and legal cost in the United States. Opioid analgesics are efficient first-line pain relievers for acute and chronic lower-extremity pain syndrome. Perioperative pain management strategies have been proposed using opioid stewardship, but there are few standardized protocols to guide podiatric medical providers treating patients with OUD. First, we describe the pharmacology of therapeutic agents used as medications for addiction treatment for OUD and substance use disorder (SUD). Second, we offer criteria for selecting acute pain and perioperative management in patients with OUD and SUD per current medical literature. Finally, we review the literature applying opioid stewardship in the context of prescribing opioid analgesics in the presence of OUD and SUD. Three hypothetical clinical scenarios grounded in clinical-based literature are described with congruent data and founded guidelines. The first and second scenarios describe acute pain and perioperative management in patients with OUD receiving methadone and buprenorphine-naloxone, respectively. The third scenario describes acute pain and perioperative management in a patient with SUD receiving intravenous naltrexone. We hope that the lower-extremity specialist will appreciate that thoughtful management of acute perioperative pain among patients who receive medications for addiction treatment for OUD is critically important given the risks of destabilization during the perioperative period. The literature reveals the lack of rigorous evidence on acute pain management in patients who receive medication for OUD; however, some clinical evidence supports the practice of continuing methadone or buprenorphine for most patients during acute pain episodes.

Postoperative Opioid-Prescribing Practice in Foot and Ankle Surgery.

BACKGROUND: Approximately 3,900 Americans die every month of opioid overdose. The total economic burden of the opioid epidemic is estimated to be more than $78 billion annually. We sought to determine whether postoperative opioid-prescribing practice variation exists in foot and ankle surgery. METHODS: We administered a voluntary, anonymous, online questionnaire consisting of six foot and ankle surgery scenarios followed by a demographics section. The purpose of the demographics section was to gather characteristics of podiatric foot and ankle surgeons. We invited podiatric foot and ankle surgeons practicing in the United States to complete the questionnaire via e-mail from the American Podiatric Medical Association's membership list. For each scenario, respondents selected the postoperative opioid(s) that they would prescribe at the time of surgery, as well as the dose, frequency, and number of "pills" (dosage units). We developed multiple linear regression models to identify associations between prescriber characteristics and two measures of opioid quantity: dosage units and morphine milligram equivalents. RESULTS: Eight hundred sixty podiatric foot and ankle surgeons completed the survey. The median number of dosage units never exceeded 30 regardless of the foot and ankle surgery. Years in practice correlated with reduction in dosage units at the time of surgery. Compared with the orthopedic community, podiatric foot and ankle surgeons prescribe approximately 25% less dosage units than orthopedic foot and ankle surgeons. CONCLUSIONS: Postoperative opioid-prescribing practice variation exists in foot and ankle surgery. Further research is warranted to determine whether additional education is needed for young surgeons.

Clinical data to be used as a foundation to combat Covid-19 vaccine hesitancy.

The coronavirus has become the paramount subject in peoples' lives, affecting and disrupting virtually every aspect of society, as the pandemic casts a shadow over the world. The facts, myths, and conspiracy theories centered on the Covid-19 pandemic have dominated social media accounts, local and national newspapers, as well as television programs. Strategies need to be evolved to counter Covid-19 vaccine hesitancy and mitigate health disparities in at-risk populations. Overcoming misinformation and distrust will require an interdisciplinary approach to deal with Covid-19. The purpose of this review is to offer a factual basis to all healthcare providers to assist in framing strategies to mitigate vaccine hesitancy and achieve herd immunity to combat the deadly Covid-19 pandemic. First an overview of the discovery of the viruses and their molecular structures will be presented. Secondly, a historical perspective is offered, comparing the differences between the 1918 flu pandemic and the current covid-19 pandemic. Lastly, an overview for proposed techniques and methods to counter and or mitigate covid-19 vaccine misinformation that may be used by an interdisciplinary team will be offered narratively and graphically.

Attitudes of eye health practitioners towards diagnostic tests and therapies for dry eye disease in Australasia.

INTRODUCTION: The diagnosis of dry eye is challenging for eye health practitioners (EHP) and recently, a variety of new diagnostic tests have emerged. This study assesses the attitudes of EHP to dry eye and testing and compares these with attitudes in 2003. METHODS: An electronic questionnaire was disseminated to EHP in Australasia between December 2020 to March 2021. Participants rated the likelihood that presenting symptoms/signs were associated with dry eye, the utility of diagnostic tests, the value of test characteristics, and their satisfaction with dry eye diagnostics. Qualitative responses were categorised into positive, negative, or neutral themes. RESULTS: 144 responses were received, with 117 (81.3%) from Australia and 27 (18.7%) from New Zealand. Posterior blepharitis was significantly more likely to be associated with dry eye than other factors (p < 0.01). Clinical history, fluorescein staining and FBUT were judged significantly more useful in diagnosing dry eye compared to other tests (p < 0.01). Test validity was judged significantly more important in choosing a test than other qualities. Qualitative attitudes towards dry eye presentations and diagnostic tests were positive in 42.2% and 24.3%, negative in 32.4% and 41.9%, and neutral in 25.5% and 33.8% respectively. CONCLUSIONS: The opinions of EHP regarding dry eye tests were variable, but most favour history and corneal staining for diagnosis. Patterns of responses were similar to that reported by Turner et al 16-years ago, however, there is a higher satisfaction with available tests and therapeutic options. There is a need to develop a consensus amongst real-world clinicians regarding an optimum diagnostic pathway for dry eye, particularly in relation to newer diagnostic tests.