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Background/AimsOptic neuritis (ON) is the primary ophthalmic manifestation of myelin oligodendrocyte glycoprotein-IgG-associated disorder (MOGAD), but numerous reports have expanded the visual manifestations of this condition. The goal of this study was to synthesise the extensive literature on this topic to help ophthalmologists understand when testing for MOG-IgG should be considered.MethodA systematic review of the English-language literature was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and searches were conducted using Ovid MEDLINE (from January 1, 1948 to April 1, 2020) and Ovid EMBASE (from January 1, 1947 to April 1, 2020). Inclusion criteria included studies describing non-isolated ON ophthalmic manifestations where cell-based assays were used for the detection of MOG antibodies.ResultsFifty-one articles representing 62 patients with a median age of 32.0 (range 2–65), female gender (51%) and follow-up of 20.0 months (range: 1–240) were included. Twenty-nine patients had non-isolated ON afferent visual manifestations: uveitis, peripheral ulcerative keratitis, acute macular neuroretinopathy, neuroretinitis, venous stasis retinopathy, large preretinal macular haemorrhage, orbital inflammatory syndrome, orbital apex syndrome, optic perineuritis, papilloedema and homonymous visual field defects. Incomplete recovery of ON was associated with a case of Leber’s hereditary optic neuropathy. Efferent ophthalmic manifestations included cranial neuropathies, internuclear ophthalmoplegia, central nystagmus, saccadic intrusions and ocular flutter. Cranial nerve involvement was secondary to enhancement of the cisternal portion or brainstem involvement. All included cases were treated with corticosteroids with 31% of cases requiring additional immunosuppressive therapy.ConclusionsMOGAD has been associated with various afferent and efferent ophthalmic manifestations apart from isolated ON. Awareness of these findings may result in earlier diagnosis and treatment.

Purpose To examine the epidemiological characteristics, trends, risk factors, management strategies, and clinical outcomes of Candida albicans and non-albicans keratitis over a 15-year period in a tertiary Canadian eye center. Methods In a retrospective observational case series of Candida keratitis from 2003 to 2017, demographics, risk factors, corrected distance visual acuity (CDVA) at initial and final consultations, medical and surgical management, and follow-up duration were recorded. Results Twenty-one cases of Candida keratitis were identified (62.5% of total fungal keratitis; 10 C. albicans and 11 non-albicans). The most commonly associated risk factors were topical steroid use (16 patients, 76%), ocular surface disease (15 patients, 71%), contact lens use (11 patients, 52%), and previous corneal surgery (8 patients, 38%); all patients had 2 or more combined risk factors. The number of patients with a visual acuity of 20/200 or better remained the same before and after the treatment (5/21, 24%). The mean duration of the antifungal treatment was 98 ± 126 days. Sixteen patients ultimately required surgical management (76%; 12 therapeutic keratoplasties, 3 enucleation, and 1 optical keratoplasty). When comparing C. albicans with non-albicans keratitis, we found no difference in presenting visual acuity, final visual acuity, or requirement for surgical management. Conclusions Candida keratitis accounts for the most identified fungal keratitis cases in this temperate climate area. An exposure to multiple risk factors appears necessary. A surgical intervention is required for the resolution of most cases. Different subspecies of Candida ultimately resulted in similar clinical outcomes.

Orofacial muscle pain is a significant clinical problem because it affects eating, speaking, and other orofacial functions in patients. However, mechanisms underlying orofacial muscle pain are not fully understood. In the present study we induced orofacial muscle pain by injecting Complete Freund's Adjuvant (CFA) into masseter muscle of rats and assessed pain by the orofacial operant test. In comparison with the control group, CFA-injected animals (CFA group) showed decreases in operant behaviors, suggesting the presence of orofacial pain. Trigeminal ganglion (TG) neurons innervating masseter muscles were retrograde-labeled with DiI and their electrophysiological properties studied using patch-clamp recordings. About 20% of DiI-labeled TG neurons showed spontaneous action potentials (APs) in the CFA group but none in the control group. AP rheobase levels were significantly lower in DiI-labeled TG neurons of the CFA group than in the control group. Membrane input resistance of DiI-labeled TG neurons was significantly higher in the CFA group than in the control group. Several other membrane parameters were also different between DiI-labeled TG neurons of the CFA and control groups. Voltage-dependent currents were examined and the most significant changes following CFA were background K+ currents, which showed significantly smaller in DiI-labeled TG neurons of CFA group compared to the control group. Collectively, orofacial muscle pain in CFA model is accompanied with changes of electrophysiological properties and background K+ currents in TG neurons that innervate masseter muscles.

Trigeminal neuropathic pain is the most debilitating pain disorder but current treatments including opiates are not effective. A common symptom of trigeminal neuropathic pain is cold allodynia/hyperalgesia or cold hypersensitivity in orofacial area, a region where exposure to cooling temperatures are inevitable in daily life. Mechanisms underlying trigeminal neuropathic pain manifested with cold hypersensitivity are not fully understood. In this study, we investigated trigeminal neuropathic pain in male rats following infraorbital nerve chronic constrictive injury (ION-CCI). Assessed by the orofacial operant behavioral test, ION-CCI animals displayed orofacial cold hypersensitivity. The cold hypersensitivity was associated with the hyperexcitability of small-sized trigeminal ganglion (TG) neurons that innervated orofacial regions. Furthermore, ION-CCI resulted in a reduction of A-type voltage-gated K+currents (IA currents) in these TG neurons. We further showed that these small-sized TG neurons expressed Kv4.3 voltage-gated K+channels, and Kv4.3 expression in these cells was significantly downregulated following ION-CCI. Pharmacological inhibition of Kv4.3 channels with phrixotoxin-2 inhibited IA-currents in these TG neurons and induced orofacial cold hypersensitivity. On the other hand, pharmacological potentiation of Kv4.3 channels amplified IA currents in these TG neurons and alleviated orofacial cold hypersensitivity in ION-CCI rats. Collectively, Kv4.3 downregulation in nociceptive trigeminal afferent fibers may contribute to peripheral cold hypersensitivity following trigeminal nerve injury, and Kv4.3 activators may be clinically useful to alleviate trigeminal neuropathic pain.SIGNIFICANCE STATEMENTTrigeminal neuropathic pain, the most debilitating pain disorder, is often triggered and exacerbated by cooling temperatures. Here, we created infraorbital nerve chronic constrictive injury (ION-CCI) in rats, an animal model of trigeminal neuropathic pain to show that dysfunction of Kv4.3 voltage-gated K+channels in nociceptive-like trigeminal ganglion (TG) neurons underlies the trigeminal neuropathic pain manifested with cold hypersensitivity in orofacial regions. Furthermore, we demonstrate that pharmacological potentiation of Kv4.3 channels can alleviate orofacial cold hypersensitivity in ION-CCI rats. Our results may have clinical implications in trigeminal neuropathic pain in human patients, and Kv4.3 channels may be an effective therapeutic target for this devastating pain disorder.

A 37-year-old woman presented with a 1-week history of painful vision loss in both eyes from optic neuritis. She was treated with intravenous, followed by oral corticosteroids. After she completed intravenous corticosteroids, she developed a new area of blurred vision inferiorly (right eye) and centrally (left eye) secondary to central serous chorioretinopathy (CSCR), which resolved after oral prednisone taper (figure). CSCR is characterized by well-circumscribed serous detachments of the retina and is typically seen after exogenous corticosteroid use. CSCR can be misdiagnosed as optic neuritis1 or develop in patients with optic neuritis after corticosteroid treatment2 and should be kept in the differential diagnosis for worsening vision after corticosteroids.

Sensitivity to cooling temperatures often becomes heightened in orofacial regions leading to orofacial cold allodynia/hyperalgesia after chronic trigeminal nerve injury. KCNQ2 channels are involved in controlling excitability of primary afferent neurons and thereby regulate sensory functions under both physiological and pathological conditions. In the present study, we sought to determine whether KCNQ2 channels in trigeminal nerves are involved in regulating orofacial operant behavioral responses to cooling stimulation. We also sought to examine whether chronic trigeminal nerve injury may alter KCNQ2 channel expression in trigeminal ganglions. Using the orofacial operant tests, animals show cold allodynia/hyperalgesia in orofacial regions following infraorbital nerve chronic constrictive injury (ION-CCI), which could be alleviated by subcutaneous administration of retigabine, a KCNQ2 activator. In contrast, subcutaneous administration of the KCNQ2 inhibitor XE991 directly elicits cold allodynia/hyperalgesia in sham animals. Using immunostaining, we show that KCNQ2 channels are primarily expressed in small-sized TG neurons. Interestingly, KCNQ2 channel expression becomes significantly upregulated in TG neurons following the ION-CCI. Our results suggest that KCNQ2 channels are involved in regulating orofacial cold sensitivity. Upregulation of KCNQ2 channels may be a compensatory change in attempting to limit injury-induced trigeminal hyperexcitability.

Long-term atherosclerotic adverse events are anticipated in patients undergoing carotid endarterectomy (CEA); however, their incidence and risk predictors remain unknown.A consecutive cohort of CEAs between 1/1/2000-12/31/2007 was analyzed. End points were any stroke, coronary event (myocardial infarction, coronary bypass, or stenting), vascular interventions for critical limb ischemia, aortic aneurysm or carotid disease, and death. Survival analysis and Cox regression models were used to identify clinical predictors.A total of 1,136 CEAs (bilateral, 89; mean age, 71.2 ± 9.2 years; 56.5% male; 36.3% symptomatic, and 3.9% combined with coronary bypass) were performed during the study period with a mean clinical follow-up of 60 months (0-155 months). The postoperative combined stroke and/or death rate was 2.7% and 1.9% for asymptomatic and 4.1% for symptomatic patients. Five and 10-year risks of the end points were 7.2% and 16.1% for stroke, 18.4% and 31.5% for coronary interventions, 20.6% and 28.5% for major vascular interventions, and 25.8% and 50.1% for death. Statins conferred a significant protective effect for stroke (hazard ratio [HR], 0.53; P = 0.016) and death (HR, 0.66; P0.0001). Baseline vascular disease predicted future vascular interventions: aortic aneurysm (HR, 1.90; P = 0.003), peripheral arterial disease (HR, 2.03; P0.0001), and contralateral internal carotid artery (ICA) stenosis ≥50% (HR, 4.61; P0.0001). Renal insufficiency predicted worse outcomes for all other end points (HR, 2.21; P = 0.023 for stroke; HR, 1.62; P = 0.008 for coronary events; HR, 2.38; P0.0001 for death).Patients undergoing CEA continue to derive long-term low stroke rate benefit but still sustain major coronary events and require vascular interventions, indicating a need for more intensive medical treatment and rigorous follow-up.

Multiple studies have evaluated the perioperative outcomes of patients with chronic renal insufficiency (CRI) undergoing carotid endarterectomy (CEA), generally indicating worse survival and cardiovascular (CV) outcomes, although not consistently and with a paucity of long-term data. The present study addresses the perioperative and long-term impact of CRI on CV events and survival after CEA.A cohort of consecutive patients treated with CEA between January 1, 2000, and December 31, 2008, was analyzed based on medical records and Social Security Death Index. Estimated glomerular filtration rate (GFR) was assessed at baseline. Renal function was used to divide patients into 3 groups: normal (GFR ≥ 60 mL/min/1.73 m(2)), moderate CRI (GFR, 30-59), and severe CRI (GFR30). The end points were major coronary events, major cerebrovascular events (any stroke), noncardiac vascular interventions (aortic disease, carotid disease, and critical limb ischemia), and mortality. Subgroup analysis based on the presence of preoperative neurologic symptoms was also performed. Survival analysis and Cox regression models were used to assess the effect of baseline predictors.A total of 1,342 CEAs (mean age, 71.2 ± 9.2 years; 55.6% male; 35.3% symptomatic) were performed during the study period with a mean clinical follow-up of 57 months (median, 55; range, 0-155 months). Eight hundred sixty-eight (65%) patients had normal renal function, 414 (31%) had moderate CRI, and 60 (4%) had severe CRI (24 on dialysis). The combined 30-day stroke/death rates for the symptomatic and asymptomatic groups were 3.2% and 1.4% (normal renal function), 5.7% and 2.6% (moderate CRI), and 14.3% and 10.3% (severe CRI), respectively, with the differences being significant only for the severe-CRI group. At 5 years, the severe-CRI group experienced significantly more coronary events (36.9% vs. 16.3%, P0.001), more cerebrovascular events (21.6% vs. 6.3%, P0.001), and deaths (70.0% vs. 20.3%, P0.001), whereas the moderate-CRI group had no significantly different outcomes compared with the normal group, except for mortality (29.8% vs. 20.3%, P0.001). After adjusting for all risk factors, severe CRI remained predictive of coronary events (hazard ratio [HR], 2.21; 95% confidence interval [CI], 1.25-3.90; P = 0.007), cerebrovascular events (HR, 3.11; 95% CI, 1.44-6.74; P = 0.004), and mortality (HR, 4.36; 95% CI, 3.00-6.34; P0.001). Symptomatology at baseline was predictive of 5-year mortality (HR, 1.43; 95% CI, 1.14-1.81; P = 0.002). The need for noncardiac vascular interventions was equally distributed among all the groups.Severe but not moderate CRI is associated with poor perioperative outcomes and is an independent predictor of CV events and death at 5 years after CEA. The decision to perform CEA in symptomatic and asymptomatic patients with severe CRI should be individualized given the poor reported outcomes.

Systemic inflammation at the development of an acute coronary syndrome (ACS) might alter the high-density lipoprotein (HDL) components and function. One of the major functions of HDL particles is their ability to remove cellular cholesterol from macrophages. The aim of the present study was to characterize the HDL efflux capacity in patients with ACS. We analyzed the cholesterol efflux in those ACS (within 72 hours of symptoms [ACS1]) and, again, 3 months later (ACS2). As controls, we used normal subjects without coronary artery disease (CAD) and patients with chronic, stable CAD. The 4 groups were matched for age and HDL cholesterol levels. We used a cell-based efflux system in (3)[H]-cholesterol-labeled J774 macrophages to measure cholesterol efflux from apolipoprotein B-depleted plasma. The present study included 20 patients with ACS. Their mean age was 58 ± 9 years, and the mean HDL cholesterol level was 1.06 ± 0.22 mmol/L (41 ± 9 mg/dl). The ACS1 group showed a marked increase in high-sensitivity C-reactive protein and serum amyloid A, reflecting systemic inflammation. The HDL cholesterol efflux capacity was reduced in ACS1 subjects and remained reduced 12 weeks later and in those with stable CAD. These results suggest that the acute presence of serum amyloid A does not account for the impairment of HDL-mediated cholesterol efflux capacity in the ACS1 group. Little correlation was found between HDL cholesterol and HDL efflux capacity (r = 0.233; p = 0.049), suggesting that HDL cholesterol is a poor marker of HDL function in inflammatory states and CAD. In conclusion, our data support the concept that atherogenic HDL dysfunction and impaired efflux occur in ACS, independent of changes in plasma HDL cholesterol and apolipoprotein A-I levels.

Purpose: To identify the characteristics predictive of unfavorable outcomes for pneumatic retinopexy (PR) in the repair of pseudophakic rhegmatogenous retinal detachments (RD). Methods: A retrospective chart review was performed at a single institution to identify patients who underwent PR in pseudophakic eyes. Pre- and postoperative data were reviewed and analyzed to evaluate predictive factors of failure. Results: Forty-four patients met the study criteria. PR was successful in 23 (52.3%) patients. The failed cases underwent scleral buckles, vitrectomies, or both. A retinal tear located outside the superior four clock hours was a significant predictor of PR failure. At six months post-intervention, the failure and success groups were statistically similar for vision and rate of reattachment. Conclusions: Modified criteria for PR in pseudophakia may include cases with retinal breaks within the superior four clock hours. If further surgery is required, the final vision and anatomic reattachment ar...

Parent education programs may be offered or mandated at various stages of the child welfare services continuum. However, little is known regarding their efficacy in addressing the parenting problems that bring families to the attention of child welfare services. This article synthesizes outcome data generated from 58 parenting programs with families determined to be at-risk of child maltreatment and/or abusive or neglectful. It places parent education programs within the broader context of research on effective parenting as well as the leading etiological models of child maltreatment to assess the evaluations of these programs with regard to methodological rigor as well as theoretical salience. Practical and theoretical implications are presented along with recommendations for future research.

Objective During the last decade, there has been a dramatic improvement in best medical treatment for patients with vascular disease. Yet, there is a paucity of contemporary long-term data for restenosis and contralateral internal carotid artery (ICA) progression. This study assessed ipsilateral and contralateral disease progression and cerebrovascular events after carotid endarterectomy (CEA). Methods A consecutive cohort of CEAs between January 1, 2000, and December 31, 2010, was retrospectively analyzed. End points were restenosis ≥50% and ≥70%, contralateral carotid disease progression (50%-69%, 70%-99%, or occlusion) and stroke. Survival analysis and Cox regression models were used to assess the effect of baseline predictors. Results During the 11-year study period, 1639 patients underwent 1782 CEAs (50.0% patch closure, 23.9% primary closure, 26.1% eversion, and 2.5% combined with coronary artery bypass grafting). The combined stroke/death rate was 2.6% overall and 1.8% in the asymptomatic cohort. The rate of restenosis ≥50% at 2, 5, and 10 years was 8.5%, 15.6%, 27.2%, and the rate for restenosis ≥70% was 3.4%, 6.5%, 10.2%, respectively. Restenosis ≥50% was predicted by hypertension (hazard ratio [HR], 2.09; P = .027), female gender (HR, 1.43; P = .042), and younger age (≤65 years; HR, 1.56; P = .016), but not by statins, surgical technique, symptoms, or other baseline risk factors. Restenoses remained asymptomatic in 125 of 148 (84.5%). Progression of contralateral ICA disease at 2, 5, and 10 years was estimated at 5.4%, 15.5%, and 46.8%, respectively. Contralateral progression was only predicted by smoking (HR, 1.74; P = .008). The stroke rate in patients with disease progression of the contralateral ICA was not different compared with those without progression (7.0% vs 3.3%; P = .063). Any-stroke rates at 2, 5, and 10 years were 4.6%, 7.3%, and 15.7%, respectively. Predictors were symptomatic lesion (HR, 1.48; P = .039), renal insufficiency, defined as a glomerular filtration rate (GFR) of 30 to 59 vs 2 (HR, 0.34; P = .009) or GFR ≥60 vs GFR 2 (HR, 0.55; P = .109), and statin use (HR, 0.59; P = .006). Conclusions Restenosis or contralateral disease progression after CEA, to a level that might warrant consideration for treatment, is very low. The potentially associated stroke rates are also very low and not clearly related to disease progression. With the exception of the postoperative duplex, surveillance within short intervals of

Background Hyperexcitability of nociceptive afferent fibers is an underlying mechanism of neuropathic pain and ion channels involved in neuronal excitability are potentially therapeutic targets. KCNQ channels, a subfamily of voltage-gated K+ channels mediating M-currents, play a key role in neuronal excitability. It is unknown whether KCNQ channels are involved in the excitability of nociceptive cold-sensing trigeminal afferent fibers and if so, whether they are therapeutic targets for orofacial cold hyperalgesia, an intractable trigeminal neuropathic pain. Methods Patch-clamp recording technique was used to study M-currents and neuronal excitability of cold-sensing trigeminal ganglion neurons. Orofacial operant behavioral assessment was performed in animals with trigeminal neuropathic pain induced by oxaliplatin or by infraorbital nerve chronic constrictive injury. Results We showed that KCNQ channels were expressed on and mediated M-currents in rat nociceptive cold-sensing trigeminal ganglion (TG) neurons. The channels were involved in setting both resting membrane potentials and rheobase for firing action potentials in these cold-sensing TG neurons. Inhibition of KCNQ channels by linopirdine significantly decreased resting membrane potentials and the rheobase of these TG neurons. Linopirdine directly induced orofacial cold hyperalgesia when the KCNQ inhibitor was subcutaneously injected into rat orofacial regions. On the other hand, retigabine, a KCNQ channel potentiator, suppressed the excitability of nociceptive cold-sensing TG neurons. We further determined whether KCNQ channel could be a therapeutic target for orofacial cold hyperalgesia. Orofacial cold hyperalgesia was induced in rats either by the administration of oxaliplatin or by infraorbital nerve chronic constrictive injury. Using the orofacial operant test, we showed that retigabine dose-dependently alleviated orofacial cold hyperalgesia in both animal models. Conclusion Taken together, these findings indicate that KCNQ channel plays a significant role in controlling cold sensitivity and is a therapeutic target for alleviating trigeminal neuropathic pain that manifests orofacial cold hyperalgesia.

Neuropathic pain induced by chemotherapy drugs such as oxaliplatin is a dose-limiting side effect in cancer treatment. The mechanisms underlying chemotherapy-induced neuropathic pain are not fully understood. KCNQ2 channels are low-threshold voltage-gated K+ channels that play a role in controlling neuronal excitability. Downregulation of KCNQ2 channels has been proposed to be an underlying mechanism of sensory hypersensitivity that leads to neuropathic pain. However, it is currently unknown whether KCNQ channels may be downregulated by chemotherapy drugs in trigeminal ganglion neurons to contribute to the pathogenesis of chemotherapy-induced orofacial neuropathic pain. In the present study, mechanical sensitivity in orofacial regions is measured using the operant behavioral test in rats treated with oxaliplatin. Operant behaviors in these animals show the gradual development of orofacial neuropathic pain that manifests with orofacial mechanical allodynia. Immunostaining shows strong KCNQ2 immunoreactivity in small-sized V2 trigeminal ganglion neurons in controls, and the numbers of KCNQ2 immunoreactivity positive V2 trigeminal ganglion neurons are significantly reduced in oxaliplatin-treated animals. Immunostaining is also performed in brainstem and shows strong KCNQ2 immunoreactivity at the trigeminal afferent central terminals innervating the caudal spinal trigeminal nucleus (Vc) in controls, but the KCNQ2 immunoreactivity intensity is significantly reduced in oxaliplatin-treated animals. We further show with the operant behavioral test that oxaliplatin-induced orofacial mechanical allodynia can be alleviated by the KCNQ2 potentiator retigabine. Taken together, these findings suggest that KCNQ2 downregulation may be a cause of oxaliplatin-induced orofacial neuropathic pain and KCNQ2 potentiators may be useful for alleviating the neuropathic pain.

Both spinal and trigeminal somatosensory systems use the TRPM8 channel as a principal transducer for detecting cold stimuli. It is currently unclear whether this cold transducer may play a role in trigeminal neuropathic pain manifesting cold allodynia and hyperalgesia. In the present study, trigeminal neuropathy was induced by chronic constrictive nerve injury of the infraorbital nerve (ION-CCI). Behavioral responses to cold stimuli in orofacial regions were assessed by the newly developed orofacial operant test in the ION-CCI rats. We tested menthol and capsazepine, two compounds that can activate and inhibit TRPM8 respectively, on orofacial operant responses to cold stimuli in ION-CCI rats. Testing animals performed operant tasks by voluntarily contacting their orofacial regions to a cold stimulation module in order to access sweetened milk as a reward, and contact time and number of the operant behaviors were automatically recorded. Total contact time was significantly reduced at the cooling temperatures of 17°C and 12°C in ION-CCI group in comparison with sham group, indicating the presence of cold allodynia and hyperalgesia in ION-CCI rats. When menthol was administered to ION-CCI rats, total contact time was further reduced and total contact number increased at the cooling temperatures. In contrast, after administration of capsazepine to ION-CCI rats, total contact time was significantly increased at the cooling temperatures. The behavioral outcomes support the idea that TRPM8 plays a role in cold allodynia and hyperalgesia following chronic trigeminal nerve injury.

Summary Family assessment instruments can enhance the clinical judgment of child welfare practitioners by structuring decision-making processes and demonstrating the linkages between assessment, service provision, and child and family outcomes. This article describes the concept of family assessment in the child welfare context and provides an overview of the theoretical and disciplinary influences in the family assessment field. Based on a structured review of 85 instruments, the article discusses 21 that appear to the be the most valid and reliable for evaluating four federally-defined domains of family assessment: (1) patterns of social interaction, (2) parenting practices, (3) background and history of the parents or caregivers, and (4) problems in access to basic necessities such as income, employment, and adequate housing. Key measurement criteria as well as practical considerations in the selection and implementation of family assessment instrumentation in child welfare are discussed.

Breathing cold air without proper temperature exchange can induce strong respiratory autonomic responses including cough, airway constriction and mucosal secretion, and can exacerbate existing asthma conditions and even directly trigger an asthma attack. Vagal afferent fiber is thought to be involved in the cold-induced respiratory responses through autonomic nerve reflex. However, molecular mechanisms by which vagal afferent fibers are excited by cold remain unknown. Using retrograde labeling, immunostaining, calcium imaging, and electrophysiological recordings, here we show that a subpopulation of airway vagal afferent nerves express TRPM8 receptors and that activation of TRPM8 receptors by cold excites these airway autonomic nerves. Thus activation of TRPM8 receptors may provoke autonomic nerve reflex to increase airway resistance. This putative autonomic response may be associated with cold-induced exacerbation of asthma and other pulmonary disorders, making TRPM8 receptors a possible target for prevention of cold-associated respiratory disorders.

Background Chronic orofacial pain conditions such as trigeminal neuropathic pain, reflex sympathetic dystrophy of the face, and temporomandibular pain disorders are debilitating pain conditions. They are known to respond poorly to treatment including opioids in human patients. There is a pressing need to better understand the mechanisms of these chronic orofacial pain conditions so that new and effective therapeutic targets can be identify. To achieve this goal, preclinical animal models that well represent human chronic orofacial pain conditions are needed. In the present study we used two preclinical models of chronic orofacial pain, the chronic constriction nerve injury of the infraorbital nerve (ION-CCI model) and the oxaliplatin-induced orofacial pain (oxaliplatin model). We applied newly developed orofacial operant behavioral assessment to study orofacial pain and to test effects on Kv7.2 channel activators in alleviating orofacial pain in these animals.

Swelling in the parotid region is often the presenting sign of a tumour of salivary gland origin. However, the possibility of disease involving adjacent structures must always be considered. Three cases are presented where pathology of the mandibular ramus presented as swelling in the parotid region. A clinical diagnosis of a parotid tumour was made, parotidectomy scheduled, and in two cases carried out before the correct diagnosis was reached. Difficulties of differential diagnosis are discussed, and imaging techniques reviewed. The value of plain radiographs of the adjacent hard tissues is emphasised. Careful interpretation should be based on a sound understanding of pathology of the jaws.