Treatment adherence to olfactory training: a real-world observational study.

BACKGROUND: Olfactory training (OT) is considered an effective intervention for most causes of smell loss and is recommended as a long-term treatment. However, the treatment adherence of OT remains unclear. This study aims to identify the frequency and causalities for lack of adherence to OT. METHODS: In this prospective study, 53 patients previously diagnosed with olfactory dysfunction (OD), who were recommended to perform OT, were enrolled. Patients underwent olfactory testing using Sniffin' Sticks for threshold, discrimination, and identification (TDI) and a subjective numeric rating scale (NRS) at a baseline and follow-up visit. In addition, patients answered a six-item treatment adherence questionnaire. The primary outcome measures were clinically relevant improvements according to the TDI (>=5.5) and NRS (>=5.5) scores. RESULTS: Out of 53 patients, 45 performed OT. Among patients who performed OT, 31% discontinued the use of OT on their own due to a self-perceived improvement, while 51% discontinued use due to lack of improvements in olfaction. In these patients, the average duration of OT use was five months. After controlling for baseline duration of OD, baseline TDI score and smell loss aetiologies, discontinuing OT due to a lack of self-perceived improvement remained significantly associated with worse TDI and NRS outcomes at follow-up. CONCLUSIONS: Our data show that therapeutical adherence to OT is low, regardless of patients' perception of olfactory function. Olfactory improvement leads to decreased training due to satisfaction, while lack of improvement leads to non-adherence based on disappointing subjective outcome. Patients should be advised to perform OT consistently.

Extreme weather conditions influence the frequency of epistaxis-related emergency room visits.

BACKGROUND: Climate change has been associated with an increase in extreme weather conditions. The aim of this study was to identify environmental factors and the effect of extreme weather events (95th percentile) on the risk for epistaxis-related emergency room visits (EV). METHODS: A total of 2179 epistaxis-related EVs were identified between 2015 and 2018. A distributed lag non-linear model was fitted to investigate the relationship between extreme weather conditions and the total number of epistaxis-related EVs per day. Cumulative relative risk (cRR) is defined as the cumulated daily risk of EV for epistaxis within a stated period after an extreme weather condition compared to the risk of EV at the median value of that weather condition. RESULTS: At a mean daily temperature of 27°C (P95), cRR for epistaxis-related EV was 2.00. At a relative humidity of 39% (P5), cRR was highest on day 3 at 1.59, while extremely high humidity (92%, P99) led to a decreased cRR of 0.7 on day 1. Intense precipitation of 24mm (P99) reduced the cRR on day 3 to 0.38. For prolonged extreme conditions over three days, extremely low wind speed, as well as both high and low atmospheric pressure events, diminished cRR. CONCLUSIONS: Extreme temperatures, relative humidity, and precipitation, as well as extended periods of extreme wind speeds and atmospheric pressure, significantly impact cRR for epistaxis-related EVs.

Position paper on olfactory dysfunction: 2023

BACKGROUND: Since publication of the original Position Paper on Olfactory Dysfunction in 2017 (PPOD-17), the personal and societal burden of olfactory disorders has come sharply into focus through the lens of the COVID-19 pandemic. Clinicians, scientists and the public are now more aware of the importance of olfaction, and the impact of its dysfunction on quality of life, nutrition, social relationships and mental health. Accordingly, new basic, translational and clinical research has resulted in significant progress since the PPOD-17. In this updated document, we present and discuss currently available evidence for the diagnosis and management of olfactory dysfunction. Major updates to the current version include, amongst others: new recommendations on olfactory related terminology; new imaging recommendations; new sections on qualitative OD and COVID-19 OD; updated management section. Recommendations were agreed by all co-authors using a modified Delphi process. CONCLUSIONS: We have provided an overview of current evidence and expert-agreed recommendations for the definition, investigation, and management of OD. As for our original Position Paper, we hope that this updated document will encourage clinicians and researchers to adopt a common language, and in so doing, increase the methodological quality, consistency, and generalisability of work in this field.

Association between olfactory function and quality of life in patients with olfactory disorders: a multicenter study in over 760 participants.

BACKGROUND: This cross-sectional, multi-centric study aimed to investigate the differences in quality of life among patients with olfactory dysfunction (OD) of different origin, and to identify factors associated with olfactory-related quality of life (QOL). METHODS: Seven hundred sixty-three adults were recruited from 8 Smell & Taste clinics in Germany, Switzerland, and Austria. Olfactory-related QOL was assessed by the Questionnaire of Olfactory Disorders (QOD). Olfactory function was assessed with the "Sniffin' Sticks" test; self-assessment was performed with visual analog scales. RESULTS: Patients with post-infectious and post-traumatic OD showed poorer olfactory-related QOL than patients with sinonasal and idiopathic OD. The olfactory-related QOL was positively associated with the "Sniffin' Sticks" test score, self-assessed olfactory function, disease duration, and age, with younger olfactory dysfunction patients showing lower QOL. Female patients presented with poorer olfactory-related QOL. In addition, the results showed that self-assessment of olfactory function explained more of the variance in olfactory-related QOL than olfactory function evaluated by the Sniffin’ Sticks test. CONCLUSIONS: In addition to the psychophysical testing results, several factors such as disease cause, disease duration, sex, or self- assessed olfactory dysfunction should be taken into account when assessing the individual severity of the smell loss.

Retronasal olfactory testing using candies sent by post and for screening purposes: a feasibility study.

BACKGROUND: The olfactory system is able to detect external odours through the orthonasal- and internal odours through the retronasal route. Flavour perception strongly relies on the sense of smell and this back route. In contrast to orthonasal, retronasal olfactory tests (ROT) are less frequently applied, although testing should be recommended for several reasons. The aim of the present investigation was to propose a suitable form of ROT for home-testing (and postal distribution) and evaluate a retronasal screening test. METHODOLOGY: Initially, 111 participants were tested using a 27-item version of the Candy Smell Test (CST). Fifty-four participants performed retesting, of which 25 subjects did so in a home-setting being supplied with professionally packed "candy-chains". Seven candies were chosen by means of hit rate differences in normosmics and severely hyposmics/anosmics. The 7-CST is designed in a non-forced-choice fashion with same seven flavours to choose from. RESULTS: For the 27-item CST both groups (subjects performing home-testing and those performing retesting at the clinic) showed highly significant test-rest-reliabilities. The 7-CST was capable of discriminating healthy from diseased subjects when being tested in 116 healthy subjects and 47 patients suffering from olfactory dysfunction. CONCLUSION: The CST is suitable for home-testing and postal distribution. The new 7-item CST can be valuable for rapidly revealing anosmics. These findings help in further standardizing ROT, may encourage rhinologists to more routinely evaluate retronasal olfactory abilities and pave the way for larger epidemiologic studies also in regard to food preferences and nutritional behaviour.

Psychological factors outmatched morphological markers in predicting limitations in activities of daily living and participation in patients with lumbar stenosis.

BACKGROUND: Recent demographic changes have led to a large population of older adults, many of whom experience degenerative disc diseases. Degenerative lumbar spinal stenosis (DLSS) is associated with considerable discomfort and limitations in activities of daily living (ADL). Symptomatic DLSS is one of the most frequent indications for spinal surgery. The aim of this study was to identify sociodemographic variables, morphological markers, depression as well as fear of movement that predict ADL performance and participation in social life in patients with DLSS. METHODS: Sixty-seven patients with DLSS (mean age 62.5 years [11.7], 50.7% females) participated in the study. Predictor variables were age, gender, duration of disease, three morphological markers (severity of the lumbar stenosis, the number of affected segments and presence of spondylolisthesis) as well as self-reported depression and fear of movement. Dependent variables were pain interference with the performance of ADLs, ADLs and participation in social life. Correlations between predictor and dependent variables were calculated before stepwise, linear regression analyses. Only significant correlations were included in the linear regression analyses. RESULTS: Variance explained by the predictor variables ranged between 12% (R2 = .12; pain interference-physical) and 40% (R2 = .40; ADL requiring lower extremity functioning; participation). Depression and fear of movement were the most powerful predictors for all dependent variables. Among the morphological markers only stenosis severity contributed to the prediction of ADLs requiring lower extremity functioning. CONCLUSION: Depression and fear of movement were more important predictors of the execution of ADLs and participation in social life compared to morphological markers. Elevated depressive symptoms and fear of movement might indicate limited adaptation and coping regarding the disease and its consequences. Early monitoring of these predictors should therefore be conducted in every spine centre. Future studies should investigate whether psychological screening or a preoperative psychological consultation helps to avoid operations and enables better patient outcomes.

Testing gustatory function using either a forced-choice or a non-forced-choice paradigm - Does it make a difference?

BACKGROUND: Recently more interest is evolving for research on gustatory function, also due to findings of â€extraoral†taste receptors with postulated participation in a pathogen detection network. Also, bitter taste function seems to be reduced in patients with chronic rhinosinusitis. For testing gustatory function â€taste strips†(TS) have been validated in a forced-choice (fc) and a non-forced-choice (nfc) paradigm and used in several studies. Purpose of the investigation was to evaluate possible differences of named modalities. METHODOLOGY: Healthy subjects (n=102) with subjective normal gustatory function and patients (n=30) with potential taste dysfunction were included. All participants were tested twice (using TS in four concentrations of sweet, sour, salty, and bitter taste), either starting with a fc or a nfc paradigm. RESULTS: In tested patients there was a difference between fc and nfc procedure with higher results for bitter in the fc testing procedure, while other qualities did not differ. This effect was also visible in the overall participants with higher scores in the fc procedure for bitter taste. CONCLUSION: TS are valid to be used in a forced and a non-forced choice paradigm, with bitter taste showing slightly higher scores in forced-choice testing. Future investigators with focus on bitter taste perception should be particularly cautious when comparing results in regard to testing procedure.

Position paper on olfactory dysfunction.

BACKGROUND: Olfactory dysfunction is an increasingly recognised condition, associated with reduced quality of life and major health outcomes such as neurodegeneration and death. However, translational research in this field is limited by heterogeneity in methodological approach, including definitions of impairment, improvement and appropriate assessment techniques. Accordingly, effective treatments for smell loss are limited. In an effort to encourage high quality and comparable work in this field, among others, we propose the following ideas and recommendations. Whilst the full set of recommendations are outlined in the main document, points include the following: - Patients with suspected olfactory loss should undergo a full examination of the head and neck, including rigid nasal endoscopy with small diameter endoscopes. - Subjective olfactory assessment should not be undertaken in isolation, given its poor reliability. - Psychophysical assessment tools used in clinical and research settings should include reliable and validated tests of odour threshold, and/or one of odour identification or discrimination. - Comprehensive chemosensory assessment should include gustatory screening. - Smell training can be helpful in patients with olfactory loss of several aetiologies. CONCLUSIONS: We hope the current manuscript will encourage clinicians and researchers to adopt a common language, and in so doing, increase the methodological quality, consistency and generalisability of work in this field.

Challenges and opportunities in developmental integrative physiology.

This review explores challenges and opportunities in developmental physiology outlined by a symposium at the 2014 American Physiological Society Intersociety Meeting: Comparative Approaches to Grand Challenges in Physiology. Across animal taxa, adverse embryonic/fetal environmental conditions can alter morphological and physiological phenotypes in juveniles or adults, and capacities for developmental plasticity are common phenomena. Human neonates with body sizes at the extremes of perinatal growth are at an increased risk of adult disease, particularly hypertension and cardiovascular disease. There are many rewarding areas of current and future research in comparative developmental physiology. We present key mechanisms, models, and experimental designs that can be used across taxa to investigate patterns in, and implications of, the development of animal phenotypes. Intraspecific variation in the timing of developmental events can be increased through developmental plasticity (heterokairy), and could provide the raw material for selection to produce heterochrony--an evolutionary change in the timing of developmental events. Epigenetics and critical windows research recognizes that in ovo or fetal development represent a vulnerable period in the life history of an animal, when the developing organism may be unable to actively mitigate environmental perturbations. 'Critical windows' are periods of susceptibility or vulnerability to environmental or maternal challenges, periods when recovery from challenge is possible, and periods when the phenotype or epigenome has been altered. Developmental plasticity may allow survival in an altered environment, but it also has possible long-term consequences for the animal. "Catch-up growth" in humans after the critical perinatal window has closed elicits adult obesity and exacerbates a programmed hypertensive phenotype (one of many examples of "fetal programing"). Grand challenges for developmental physiology include integrating variation in developmental timing within and across generations, applying multiple stressor dosages and stressor exposure at different developmental timepoints, assessment of epigenetic and parental influences, developing new animal models and techniques, and assessing and implementing these designs and models in human health and development.

Critical windows in embryonic development: Shifting incubation temperatures alter heart rate and oxygen consumption of Lake Whitefish (Coregonus clupeaformis) embryos and hatchlings.

Critical windows are periods of developmental susceptibility when the phenotype of an embryonic, juvenile or adult animal may be vulnerable to environmental fluctuations. Temperature has pervasive effects on poikilotherm physiology, and embryos are especially vulnerable to temperature shifts. To identify critical windows, we incubated whitefish embryos at control temperatures of 2°C, 5°C, or 8°C, and shifted treatments among temperatures at the end of gastrulation or organogenesis. Heart rate (fH) and oxygen consumption ( [Formula: see text] ) were measured across embryonic development, and [Formula: see text] was measured in 1-day old hatchlings. Thermal shifts, up or down, from initial incubation temperatures caused persistent changes in fH and [Formula: see text] compared to control embryos measured at the same temperature (2°C, 5°C, or 8°C). Most prominently, when embryos were measured at organogenesis, shifting incubation temperature after gastrulation significantly lowered [Formula: see text] or fH. Incubation at 2°C or 5°C through gastrulation significantly lowered [Formula: see text] (42% decrease) and fH (20% decrease) at 8°C, incubation at 2°C significantly lowered [Formula: see text] (40% decrease) and fH (30% decrease) at 5°C, and incubation at 5°C and 8°C significantly lowered [Formula: see text] at 2°C (27% decrease). Through the latter half of development, [Formula: see text] and fH in embryos were not different from control values for thermally shifted treatments. However, in hatchlings measured at 2°C, [Formula: see text] was higher in groups incubated at 5°C or 8°C through organogenesis, compared to 2°C controls (43 or 65% increase, respectively). Collectively, these data suggest that embryonic development through organogenesis represents a critical window of embryonic and hatchling phenotypic plasticity. This study presents an experimental design that identified thermally sensitive periods for fish embryos.

Intranasal insulin influences the olfactory performance of patients with smell loss, dependent on the body mass index: A pilot study.

BACKGROUND: The application of intranasal insulin in healthy humans has been linked to improved memory function, reduced food intake, and increased olfactory thresholds. There has also been some correlation between the morbidities associated with central nervous system (CNS) insulin resistance, such as type II diabetes mellitus, Alzheimer's disease, obesity, and impaired odour recognition. Given that impaired odour recognition is an important component of olfactory performance, mechanisms that govern these effects may account for impaired olfactory functions in anosmic patients. METHODOLOGY: Ten patients with post-infectious olfactory loss received intranasal administration of 40 IU insulin or a placebo solution, as well as olfactory performance tests before and after administration. RESULTS: When administered insulin, patients exhibited an immediate performance improvement with regard to olfactory sensitivity and olfactory intensity ratings. In addition, more odours were correctly identified. Furthermore, an improvement in the odour identification task was detected in patients with higher body mass index. CONCLUSION: Results of this pilot study shed light on the link between cerebral insulin level and an impaired sense of smell. This research line might provide a better understanding of olfactory loss in relation to eating and dietary behavior, and could offer opportunities to develop faster therapeutic intervention for patients with olfactory dysfunction.

Embryonic development of lake whitefish Coregonus clupeaformis: a staging series, analysis of growth and effects of fixation.

A reference staging series of 18 morphological stages of laboratory reared lake whitefish Coregonus clupeaformis is provided. The developmental processes of blastulation, gastrulation, neurulation as well as development of the eye, circulatory system, chromatophores and mouth are included and accompanied by detailed descriptions and live imaging. Quantitative measurements of embryo size and mass were taken at each developmental stage. Eggs were 3·19 ± 0·16 mm (mean ± s.d.) in diameter at fertilization and embryos reached a total length (LT ) of 14·25 ± 0·41 mm at hatch. Separated yolk and embryo dry mass were 0·25 ± 0·08 mg and 1·39 ± 0·17 mg, respectively, at hatch. The effects of two common preservatives (formalin and ethanol) were examined throughout development and post hatch. Embryo LT significantly decreased following fixation at all points in development. A correction factor to estimate live LT from corresponding fixed LT was determined as live LT = (fixed LT )(1·025) . Eye diameter and yolk area measurements significantly increased in fixed compared with live embryos up to 85-90% development for both measurements. The described developmental stages can be generalized to teleost species, and is particularly relevant for the study of coregonid development due to additionally shared developmental characteristics. The results of this study and staging series are therefore applicable across various research streams encompassing numerous species that require accurate staging of embryos and descriptions of morphological development.

Intranasal trigeminal sensitivity: measurements before and after nasal surgery.

Nasal surgeries constitute an extensive manipulation of the nasal mucosa and therefore of structures related to trigeminal and olfactory sensitivity. While olfactory changes due to nasal surgery are relatively well investigated, there are only very few studies regarding trigeminal sensitivity. Aim of the present study was to investigate sensory changes after nasal surgery with special regard to the trigeminal sensitivity. In 38 patients prior to and around 12 weeks after nasal surgery the following psychophysical measures were performed: odor identification, odor discrimination, phenyl ethyl alcohol odor threshold, sensitivity to trigeminal stimuli, trigeminal detection thresholds and trigeminal pain thresholds. These results were compared to those of a control group (43 healthy volunteers). Psychophysical olfactory and trigeminal testing showed no major changes in patients after surgery compared to the control group. Independent from the time of measurement higher trigeminal detection thresholds were found in patients compared to healthy subjects, meaning that trigeminal thresholds were already increased before surgery. The present study revealed a decreased trigeminal sensitivity in patients already before surgery. It may be hypothesized that patients also exhibit a decreased sensitivity for nasal airflow, which may also contribute to the patients' impression of impaired nasal breathing.

Randomized controlled trial of 2.5-cm versus 3.5-cm mesial temporal resection--Part 2: volumetric resection extent and subgroup analyses.

BACKGROUND: This paper is addressing outcome differences in interesting subgroups from a previous randomized controlled trial of the extent of mesial temporal lobe resection (TLR) for drug-resistant epilepsy, by looking at effects of randomization, intended resection group, center, and true resection extent on seizure outcome. METHODS: One hundred and seventy-nine cases with volumetrically assessed resection extent were used. Analyses of the extent of resection and subgroups and within subgroups for the two treatment arms will be performed, looking for confounding factors and using statistical methods (chi-square test, logistic regression analysis, and two-factorial ANOVA). RESULTS: True resection extent varied considerably. Outcome comparison for right versus left resections, subgroups with mesial temporal sclerosis (MTS), or largest and smallest resections revealed no remarkable difference, compared to overall class I outcome. The intent-to-treat analyses within these subgroups revealed differences for class I outcome, albeit lacking in significance, except for better TLR outcome. Small true resection volume differences or randomization into the two resection groups could not explain the outcome differences between the selective amygdalohippocampectomy (SAH) and TLR subgroups. Logistic regression analysis showed an interaction between intended resection length and surgery type, confirming the impression of different impacts of the intended resection length under the two surgery types. The outcome difference between SAH and TLR was more likely explained by a center effect. In a two-factorial ANOVA for resected hippocampal volume, Engel outcome class I, and resection type, the outcome was not found to be correlated with true resection volume. A multifactorial logistic regression showed a mild interaction between the resection type with center on the Engel outcome class, extent of resection, and surgery type interacted, as did the extent of resection and center. CONCLUSION: Patients with quite similar extent of resection can be seizure free or non-seizure free. In this cohort, seizure freedom rates fell again when the extent of mesial resection was maximized. Differences in class I outcome for SAH and TLR were not due to erroneous randomization, true resection extent, or presence of MTS, but were influenced by a center effect. Subgroup analyses did not help to provide arguments to favor one surgery type over the other.

Randomized controlled trial of 2.5-cm versus 3.5-cm mesial temporal resection in temporal lobe epilepsy--Part 1: intent-to-treat analysis.

BACKGROUND: Only one prospective randomized study on the extent of mesial resection in surgery for temporal lobe epilepsy (TLE) exists. This randomized controlled trial (RCT) examines whether 3.5-cm mesial resection is leading to a better seizure outcome than a 2.5-cm resection. METHODS: Three epilepsy surgery centers using similar MRI protocols, neuropsychological tests, and resection types for TLE surgery included 207 patients in a RCT with pre- and postoperative volumetrics. One hundred and four patients were randomized into a 2.5-cm resection group and 103 patients into a 3.5-cm resection group, i.e., an intended minimum resection length of 25 versus 35 mm for the hippocampus and parahippocampus. Primary outcome measure was seizure freedom Engel class I throughout the first year. The study was powered to detect a 20% difference in class I outcome. Seizure outcome was available for 207 patients, complete volumetric results for 179 patients. Outcome analysis was restricted to control of successful randomization and an intent-to-treat analysis of seizure outcome. RESULTS: The mean true resection volumes were significantly different for the 2.5-cm and 3.5-cm resection groups; thus, the randomization was successful. Median resection volume in the 2.5-cm group was 72.86% of initial volume and 83.44% in the 3.5-cm group. At 1 year, seizure outcome Engel class I was 74% in the 2.5-cm and 72.8% in the 3.5-cm resection group. CONCLUSIONS: The primary intent-to-treat analysis did not show a different seizure freedom rate for the more posteriorly reaching 3.5-cm resection group. It appears possible that not maximal volume resection but adequate volume resection leads to good seizure freedom.

Complicated sigmoid diverticulitis--Hartmann's procedure or primary anastomosis?

INTRODUCTION: Diverticular disease of the colon is a common condition in developed countries. For perforated diverticulitis Hartmann's procedure is a safe and quick treatment option. But intestinal restoration needs further interventions. This leads to high complication rates and cost. Therefore a critical evaluation of surgical treatment options is necessary. METHODS: During a period of 18 months 88 patients underwent surgical resection for diverticulitis. Forty patients had emergency surgery. Among those a primary anastomosis was performed in 21 patients. The other 19 patients had interval colostomy. Among 21 patients with primary anastomosis major complications occurred in two patients, vs. twelve in patients with Hartmann's operation (p = 0.03). In the Hartmann group eight patients had major general complications, vs. one patient in the group with primary anastomosis (p = 0.06). The mean hospital stay was 38 days after Hartmann's procedure, vs. 13 days for patients with primary anastomosis (p < 0.01). CONCLUSION: In emergency surgery for complicated diverticulitis primary anastomosis is not associated with an increased postoperative morbidity. A primary anastomosis reduces the need for further surgical interventions and complex re-operations. Thus, an overall reduction of morbidity, cost, complication rate and hospital stay is possible. Therefore this technique is advantageous for patients and hospitals.

Decreased angiogenesis as a possible pathomechanism in cervical degenerative myelopathy.

Endogenous immune mediated reactions of inflammation and angiogenesis are components of the spinal cord injury in patients with degenerative cervical myelopathy (DCM). The aim of this study was to identify alteration of certain mediators participating in angiogenetic and inflammatory reactions in patients with DCM. A consecutive series of 42 patients with DCM and indication for surgical decompression were enrolled for the study. 28 DCM patients were included, as CSF samples were taken preoperatively. We enrolled 42 patients requiring surgery for a thoracic abdominal aortic aneurysm (TAAA) as neurologically healthy controls. In 38 TAAA patients, CSF samples were taken prior to surgery and thus included. We evaluated the neurological status of patients and controls prior to surgery including NDI and mJOA. Protein-concentrations of factors with a crucial role in inflammation and angiogenesis were measured in CSF via ELISA testing (pg/ml): Angiopoietin 2, VEGF-A and C, RANTES, IL 1 beta and IL 8. Additionally, evaluated the status of the blood-spinal cord barrier (BSCB) by Reibers´diagnostic in all participants. Groups evidently differed in their neurological status (mJOA: DCM 10.1 ± 3.3, TAAA 17.3 ± 1.2, p < .001; NDI: DCM 47.4 ± 19.7, TAAA 5.3 ± 8.6, p < .001). There were no particular differences in age and gender distribution. However, we detected statistically significant differences in concentrations of mediators between the groups: Angiopoietin 2 (DCM 267.1.4 ± 81.9, TAAA 408.6 ± 177.1, p < .001) and VEGF C (DCM 152.2 ± 96.1, TAAA 222.4 ± 140.3, p = .04). DCM patients presented a mild to moderate BSCB disruption, controls had no signs of impairment. In patients with DCM, we measured decreased concentrations of angiogenic mediators. These results correspond to findings of immune mediated secondary harm in acute spinal cord injury. Reduced angiogenic activity could be a relevant part of the pathogenesis of DCM and secondary harm to the spinal cord.

The type III secretion system tip complex and translocon.

The type III secretion machinery of Gram-negative bacteria, also known as the injectisome or needle complex, is composed of a basal body spanning both bacterial membranes and the periplasm, and an external needle protruding from the bacterial surface. A set of three proteins, two hydrophobic and one hydrophilic, are required to allow translocation of proteins from the bacterium to the host cell cytoplasm. These proteins are involved in the formation of a translocation pore, the translocon, in the host cell membrane. Exciting progress has recently been made on the interaction between the translocators and the injectisome needle and the assembly of the translocon in the host cell membrane. As expected, the two hydrophobic translocators insert into the target cell membrane. Unexpectedly, the third, hydrophilic translocator, forms a complex on the distal end of the injectisome needle, the tip complex, and serves as an assembly platform for the two hydrophobic translocators.

Cervical spondylotic myelopathy: Changes of fractional anisotropy in the spinal cord and magnetic resonance spectroscopy of the primary motor cortex in relation to clinical symptoms and their duration.

OBJECTIVE: To determine the changes in fractional anisotropy (FA) at the proximal spinal cord and in magnetic resonance spectroscopy (MRS) of the precentral gyrus in patients with cervical spondylotic myelopathy (CSM) with respect to clinical symptoms and their duration. MATERIAL AND METHODS: 20 patients with CSM (7 female; mean age 64.6 ± 10.5 years) and 18 age/sex matched healthy controls (9 female; mean age 63.5 ± 6.6 years) were prospectively included. Clinical data (modified Japanese Orthopaedic Association Score (mJOA) and Neck Disability Index (NDI)) and 3T MR measurements including DTI at the spinal cord (level C2/3) with FA and MRS of the left and right precentral gyrus were taken. Clinical correlations and regression analyses were performed. RESULTS: Mean clinical scores of patients were significantly different to controls (mJOA; CSM: 10.2 ± 2.9; controls: 18.0 ± 0.0, p < 0.001; NDI; CSM: 41.4±23.5; controls: 4.4±6.6, p<0.001); FA was significantly lower in patients (CSM: 0.645 ± 0.067; controls: 0.699 ± 0.037, p = 0.005). MRS showed significantly lower metabolite concentrations between both groups: creatine (Cr) (CSM: 46.46±7.64; controls: 51.36±5.76, p = 0.03) and N-acetylaspartate (NAA) (CSM: 93.94±19.22; controls: 107.24±20.20, p = 0.05). Duration of symptoms ≤6 months was associated with increased myo-inositol (Ins) (61.58±17.76; 44.44±10.79; p = 0.02) and Ins/Cr ratio (1.36±0.47; 0.96±0.18; p = 0.014) compared to symptoms >6 months. CONCLUSION: Metabolic profiles of the precentral gyrus and FA in the uppermost spinal cord differ significantly between patients and healthy controls. Ins, thought to be a marker of endogenous neuroinflammatory response, is high in the early course of CSM and normalizes over time.

Position paper on olfactory dysfunction.

Background: Olfactory dysfunction is an increasingly recognised condition, associated with reduced quality of life and major health outcomes such as neurodegeneration and death. However, translational research in this field is limited by heterogeneity in methodological approach, including definitions of impairment, improvement and appropriate assessment techniques. Accordingly, effective treatments for smell loss are limited. In an effort to encourage high quality and comparable work in this field, among others, we propose the following ideas and recommendations. Whilst the full set of recommendations are outlined in the main document, points include the following: • Patients with suspected olfactory loss should undergo a full examination of the head and neck, including rigid nasal endoscopy with small diameter endoscopes. • Subjective olfactory assessment should not be undertaken in isolation, given its poor reliability. • Psychophysical assessment tools used in clinical and research settings should include reliable and validated tests of odour threshold, and/or one of odour identification or discrimination. • Comprehensive chemosensory assessment should include gustatory screening. • Smell training can be helpful in patients with olfactory loss of several aetiologies. Conclusions: We hope the current manuscript will encourage clinicians and researchers to adopt a common language, and in so doing, increase the methodological quality, consistency and generalisability of work in this field.