'It's just a mucocele': a case report of a massive appendiceal mucocele presenting as a left upper quadrant mass.

Tumours of the appendix are very rare tumours that can and often present with a mucocele. This is a case report highlighting the associated pathology of appendix tumours and the management of a large mucocele. Specifically, how a right hemicolectomy is very rarely needed in these cases regardless of size and local anatomical relationships and some important considerations for the practicing surgeon in the non-tertiary centre that encounters a case like this.

Projections of the densocellular part of the hyperpallium in the rostral Wulst of pigeons (Columba livia).

The Wulst in birds shows a four-layered structure: apical part of the hyperpallium (HA), interstitial part of HA (IHA), intercalated part of hyperpallium (HI), and densocellular part of hyperpallium (HD). The Wulst consists of a small rostral somatosensory region and a larger caudal visual region. The visual HD relays visual information to IHA and HA in the Wulst and also transfers visual information to the hippocampal formation (Atoji et al., J Comp Neurol 526: 146-165, 2018). However, fiber pathways of the rostral HD remain unknown. In the present study, the fiber connections of the rostral HD and overlying HI were analyzed with tract-tracing techniques using a combination of injections of cholera toxin subunit B (CTB) for retrograde tracing and biotinylated dextran amine (BDA) for anterograde tracing. When the two tracers were bilaterally but separately injected into the rostral HD, major reciprocal connections were seen with the rostral HA, prepiriform cortex, and subdivisions of the hippocampal formation. One-way projections of huge fibers also reached the medial part of the medial striatum. When CTB and BDA were bilaterally and separately injected into the rostral HI, strong reciprocal connections were found between the rostral HI and HA, and weak connections were seen with areas outside the Wulst. These results suggest that the fiber pathways of the rostral HD and HI are distinguishable from each other in the telencephalon and suggest also that the rostral HD relays information to the rostral HA and simultaneously acts as a mediator to the hippocampal formation.

Female Songbirds: The unsung drivers of courtship behavior and its neural substrates.

Songbirds hold a prominent role in the fields of neurobiology, evolution, and social behavior. Many of these fields have assumed that females lacked the ability to produce song and have therefore treated song as a male-specific behavior. Consequently, much of our understanding regarding the evolution and neural control of song behavior has been driven by these assumptions. Here we review literature from diverse fields to provide a broader perspective of the role of females in vocal communication and courtship. Recent evidence indicates that song evolved in both males and females and instances of female song are still common. The specialized neural circuit known as the "song system," which is necessary for singing in males, is also present in females, including those that do not sing, implying broader functions that include evaluating male song and controlling courtship behavior. In addition to having flexible, individualized preferences, females actively shape their social network through their interactions with males, females, and juveniles. We suggest that by developing more accurate hypotheses concerning the role of females we may better understand the evolution and neural mechanisms of song production and courtship behavior.

Ovarian Teratocarcinoma in an Emu (Dromaius novaehollandiae): Histopathological and Immunohistochemical Characterization.

A 17-year-old female emu (Dromaius novaehollandiae) was presented for clinical evaluation due to a 3-week history of anorexia and progressive weight loss. The emu died after sedation. At necropsy examination, the ovary and the majority of the oviduct were effaced by a multinodular cystic mass and accompanied by 6 l of coelomic effusion. Histopathology revealed a neoplasm composed of well-differentiated, poorly organized tissues derived from ectoderm, mesoderm and endoderm. Tissues within the neoplasm expressed glial fibrillary acidic protein, desmin and cytokeratins AE1/AE3, respectively, confirming the diagnosis of teratocarcinoma.

Supporting doctors as healthcare quality and safety advocates: Recommendations from the Association of Surgeons in Training (ASiT).

BACKGROUND: As front-line healthcare staff, doctors in surgical training occupy a unique organisational space rotating through hospitals and services in which they witness first hand both good and bad practice. This puts trainees in a clear position to identify and raise patient safety issues, and to contribute to discussions regarding quality and safety improvement. However, there are a number of real and perceived barriers to trainees doing so. These include concerns about the impact on training assessments and career progression, and uncertainty about the appropriate route. METHODS: Paper-based survey of delegates attending the Association of Surgeons in Training (ASiT) conference (response rate 73%; 479/652). RESULTS: 288 (60%) of trainees reported previous concerns over practices and behaviour of colleagues that might pose risks to patient care including concerns over poor performance (n = 243; 84%), bullying (n = 45; 16%), alcohol and drug abuse (n = 15; 5%) and mental health problems (n = 8; 3%). However, 53% (n = 153) did not escalate these concerns. 178 (37%) of trainees also reported concerns over hospital policies, protocols or systems that might pose a risk to patient care, with 46% (n = 82) not escalating such concerns. Respondents highlighted fear of personal vilification or reprisal (n = 224; 47%), fear of impact on career (n = 206; 43%) and a lack of confidence in the process (n = 170; 36%) as barriers to whistleblowing. More senior trainees were significantly more likely to raise concerns than more junior grades (p < 0.0001). CONCLUSION: These results highlight worrying issues around reporting concerns, with trainees often "silent witnesses" to poor performance in healthcare. Adverse events must provide opportunities for learning to improve future outcomes. Herein, ASiT proposes 14 recommendations to improve protection for trainees in raising patient safety concerns. These include the creation of a positive workplace culture, promoting the active involvement of trainees in quality improvement discussions, with clear mechanisms for trainees to raise concerns.

A systematic review of the incidence of and risk factors for postoperative atrial fibrillation following general surgery.

Atrial fibrillation is a common cardiac arrhythmia and can occur de novo following a surgical procedure. It is associated with increased inpatient and long-term mortality. There is limited evidence concerning new-onset atrial fibrillation following abdominal surgery. This study aimed to identify the prevalence of and risk factors for postoperative atrial fibrillation in the general surgical population. A systematic search of the Embase, MEDLINE and Cochrane (CENTRAL) databases was conducted. Studies were included in the review if they reported cases of new-onset atrial fibrillation within 30 days of the index operation. Results were evaluated qualitatively due to substantial clinical heterogeneity. Incidence rates were pooled using a weighted random-effects meta-analysis model. A total of 835 records were initially identified, from which 32 full texts were retrieved. Following review, 13 studies were included that involved 52,959 patients, of whom 10.94% (95%CI 7.22-15.33) developed atrial fibrillation. Five studies of patients undergoing oesophagectomy (n = 376/1923) had a weighted average rate of 17.66% (95%CI 12.16-21.47), compared with 7.63% (95%CI 4.39-11.98) from eight studies of non-oesophageal surgery (n = 2927/51,036). Identified risk factors included: increasing age; history of cardiac disease; postoperative complications, particularly, sepsis, pneumonia and pleural effusions. New-onset postoperative atrial fibrillation is common, and is more frequent after surgery involving the thorax. Future work should focus on stratifying risk to allow targeted prophylaxis of atrial fibrillation and other peri-operative complications.

Non-invasive methods for estimating mPAP in COPD using cardiovascular magnetic resonance imaging.

PURPOSE: Pulmonary hypertension (PH) is associated with a poor outcome in chronic obstructive pulmonary disease (COPD) and is diagnosed invasively. We aimed to assess the diagnostic accuracy and prognostic value of non-invasive cardiovascular magnetic resonance (CMR) models. METHODS: Patients with COPD and suspected PH, who underwent CMR and right heart catheter (RHC) were identified. Three candidate models were assessed: 1, CMR-RV model, based on right ventricular (RV) mass and interventricular septal angle; 2, CMR PA/RV includes RV mass, septal angle and pulmonary artery (PA) measurements; 3, the Alpha index, based on RV ejection fraction and PA size. RESULTS: Of 102 COPD patients, 87 had PH. The CMR-PA/RV model had the strongest diagnostic accuracy (sensitivity 92%, specificity 80%, positive predictive value 96% and negative predictive value 63%, AUC 0.93, p<0.0001). Splitting RHC-mPAP, CMR-RV and CMR-PA/RV models by 35mmHg gave a significant difference in survival, with log-rank chi-squared 5.03, 5.47 and 7.10. RV mass and PA relative area change were the independent predictors of mortality at multivariate Cox regression (p=0.002 and 0.030). CONCLUSION: CMR provides diagnostic and prognostic information in PH-COPD. The CMR-PA/RV model is useful for diagnosis, the RV mass index and PA relative area change are useful to assess prognosis. KEY POINTS: • Pulmonary hypertension is a marker of poor outcome in COPD. • MRI can predict invasively measured mean pulmonary artery pressure. • Cardiac MRI allows for estimation of survival in COPD. • Cardiac MRI may be useful for follow up or future trials. • MRI is potentially useful to assess pulmonary hypertension in patients with COPD.

Differential projections of the densocellular and intermediate parts of the hyperpallium in the pigeon (Columba livia).

The visual Wulst in birds shows a four-layered structure: apical part of the hyperpallium (HA), interstitial part of HA (IHA), intercalated part of hyperpallium (HI), and densocellular part of hyperpallium (HD). HD also connects with the hippocampus and olfactory system. Because HD is subjacent to HI, the two have been treated as one structure in many studies, and the fiber connections of HD have been examined by afferents and efferents originating outside HD. However, to clarify the difference between these two layers, they need to be treated separately. In the present study, the fiber connections of HD and HI were analyzed with tract-tracing techniques using a combination of injections of cholera toxin subunit B (CTB) for retrograde tracing and biotinylated dextran amine (BDA) for anterograde tracing. When the two tracers were bilaterally injected in HD, a major reciprocal connection was seen with the dorsolateral subdivision (DL) of the hippocampal formation. When CTB and BDA were bilaterally injected in HI, strong reciprocal connections were found between HI and HA. Next, projection neurons in HD and HI were examined by double staining for CTB combined with vesicular glutamate transporter 2 (vGluT2) mRNA in situ hybridization. After CTB was injected in DL or HA, many neurons revealed CTB+/vGluT2+ in HD or HI, respectively. Furthermore, in situ hybridization showed that DL and HA contained neurons expressing various subunits of ionotropic glutamate receptors: AMPA, kainate, and NMDA types. These results suggest that glutamatergic neurons in HD and HI project primarily to DL and HA, respectively.

Is it time for one-step nucleic acid amplification (OSNA) in colorectal cancer? A systematic review and meta-analysis.

BACKGROUND: Lymph node metastasis (LNM) is prognostic in colorectal cancer (CRC). However, evaluation by routine haematoxylin and eosin histology (HE) limits nodal examination and is subjective. Missed LNMs from tissue allocation bias (TAB) might under-stage disease, leading to under-treatment. One-step nucleic acid amplification (OSNA) for CK19 messenger ribonucleic acid (mRNA), a marker of LNM, analyses the whole node. The aim of the present systematic review and meta-analysis was to assess recent studies on OSNA versus HE and its implications for CRC staging and treatment. METHODS: Databases including OVID, Medline and Google Scholar were searched for OSNA, LNM and CRC. Study results were pooled using a random-effects model. Summary receiver operator curves (SROC) assessed OSNA's performance in detecting LNM when compared to routine HE histology. RESULTS: Five case-control studies analysing 4080 nodes from 622 patients were included. The summary estimates of pooled results for OSNA were sensitivity 0.90 [95% confidence interval (CI) 0.86-0.93], specificity 0.94 (95% CI 0.93-0.95) and diagnostic odds ratio 179.5 (CI 58.35-552.2, p < 0.0001). The SROC curve indicated a maximum joint sensitivity and specificity of 0.88 and area under the curve of 0.94, p < 0.0001. On average, 5.4% HE-negative nodes were upstaged by OSNA. CONCLUSIONS: OSNA is as good as routine HE. It may avoid TAB and offer a more objective and standardised assay of LNM. However, for upstaging, its usefulness as an adjunct to HE or superiority to HE requires further assessment of the benefits, if any, of adjuvant therapy in patients upstaged by OSNA.

Dynamical Defects in Rotating Magnetic Skyrmion Lattices.

The chiral magnet Cu_{2}OSeO_{3} hosts a Skyrmion lattice that may be equivalently described as a superposition of plane waves or a lattice of particlelike topological objects. A thermal gradient may break up the Skyrmion lattice and induce rotating domains, raising the question of which of these scenarios better describes the violent dynamics at the domain boundaries. Here, we show that in an inhomogeneous temperature gradient caused by illumination in a Lorentz transmission electron microscope different parts of the Skyrmion lattice can be set into motion with different angular velocities. Tracking the time dependence, we show that the constant rearrangement of domain walls is governed by dynamic 5-7 defects arranging into lines. An analysis of the associated defect density is described by Frank's equation and agrees well with classical 2D Monte Carlo simulations. Fluctuations of boundaries show a surgelike rearrangement of Skyrmion clusters driven by defect rearrangement consistent with simulations treating Skyrmions as point particles. Our findings underline the particle character of the Skyrmion.

Innervation of the syrinx of the zebra finch (Taeniopygia guttata).

In songbirds, the learning and maintenance of song is dependent on auditory feedback, but little is known about the presence or role of other forms of sensory feedback. Here, we studied the innervation of the avian vocal organ, the syrinx, in the zebra finch. Using a combination of immunohistochemistry, immunofluorescence and neural tracing with subunit B of cholera toxin (CTB), we analysed the peripheral and central endings of the branch of the hypoglossal nerve that supplies the syrinx, the tracheosyringeal nerve. In the syringeal muscles, we show the presence of numerous choline acetyl transferase-like immunoreactive en plaque motor endplates and substance P-like immunoreactive, thin and varicose free nerve endings. Substance P-like immunoreactive free nerve endings were also present in the luminal syringeal tissues, especially in the luminal epithelium of the trachea and pessulus. Also, by a combination of immunofluorescence and transganglionic tracing following injections of CTB in the tracheosyringeal nerve, we identified as central targets of the syringeal receptors the caudolateral part of the interpolaris subnucleus of the descending trigeminal tract, a caudolateral region of the nucleus tractus solitarius, and a lateral band of the principal sensory trigeminal nucleus. Further studies are required to determine the sensory modalities of these receptors and the connections of their specific synaptic targets.

The sensory trigeminal complex and the organization of its primary afferents in the zebra finch (Taeniopygia guttata).

Our knowledge of the avian sensory trigeminal system has been largely restricted to the principal trigeminal nucleus (PrV) and its ascending projections to the forebrain. Studies addressing the cytoarchitecture and organization of afferent input to the sensory trigeminal complex, which includes both the PrV and the nuclei of the descending trigeminal tract (nTTD), have only been performed in pigeons and ducks. Here we extend such an analysis to a songbird, the zebra finch (Taeniopygia guttata). We describe the cytoarchitecture of the sensory trigeminal complex, the patterns of calbindin-like and substance P-like immunoreactivity, and the organization of afferents from the three branches of the trigeminal nerve and from the lingual branch of the hypoglossal nerve. On the basis of cytoarchitecture and immunohistochemistry, the sensory trigeminal column can be subdivided from caudal to rostral, as in other species, into cervical dorsal horn, subnucleus caudalis, subnucleus interpolaris, subnucleus oralis, and nucleus principalis. The relative positions of the terminal fields of the three trigeminal branches move from medial to lateral in the dorsal horn to dorsomedial to ventrolateral in nTTD, whereas in PrV there is considerable overlap of mandibular and ophthalmic terminal fields, with only a small maxillary input ventrally. The hypoglossal afferents, which terminate medially in the dorsal horn and dorsolaterally in nTTD, terminate in specific cell groups in the dorsolateral nTTDo and in PrV. This work sets the grounds for further analyses of the ascending connections of the nTTD and the afferents from the syrinx to the trigeminal sensory column.

The ascending projections of the nuclei of the descending trigeminal tract (nTTD) in the zebra finch (Taeniopygia guttata).

In our traditional view of the avian somatosensory system, input from the beak and head reaches the telencephalon via a disynaptic pathway, involving projections from the principal sensory nucleus (PrV) directly to nucleus basorostralis (previously called nucleus basalis), whereas input from the rest of the body follows a trisynatic pathway similar to that in mammals, involving projections from the dorsal column nuclei to the thalamus, and thence to somatosensory wulst. However, the role of the nuclei of the descending trigeminal tract (nTTD) in this scenario is unclear, partly because their ascending projections have been examined in only one species, the mallard duck. Here we examine the ascending projections of the nTTD in the zebra finch, using in vivo injections of biotinylated dextran amine and verification of projections by means of retrograde transport of the beta subunit of cholera toxin. The results show a high degree of interconnectivity within the nTTD, and that these nuclei project to PrV. We also find a projection from nTTD to the contralateral thalamic nucleus uvaeformis, a multi-sensory nucleus connected to the song system. Furthermore, our finding of a projection from nTTD to the contralateral somatosensory thalamic nucleus dorsalis intermedius ventralis anterior (DIVA) is consistent with the well-known projection in mammals from nTTD to the ventrobasal thalamus, suggesting that the ascending trigeminal pathways in birds and mammals are more similar than previously thought.

The ventromedial hypothalamic nucleus in the zebra finch (Taeniopygia guttata): Afferent and efferent projections in relation to the control of reproductive behavior.

Sex-specific mating behaviors occur in a variety of mammals, with the medial preoptic nucleus (POM) and the ventromedial hypothalamic nucleus (VMH) mediating control of male and female sexual behavior, respectively. In birds, likewise, POM is predominantly involved in the control of male reproductive behavior, but the degree to which VMH is involved in female reproductive behavior is unclear. Here, in male and female zebra finches, a combination of aromatase immunohistochemistry and conventional tract tracing facilitated the definition of two separate but adjacent nuclei in the basal hypothalamus: an oblique band of aromatase-positive (AR+) neurons, and ventromedial to this, an ovoid, aromatase-negative (AR-) nucleus. The AR- nucleus, but not the AR+ nucleus, was here shown to receive a projection from rostral parts of the thalamic auditory nucleus ovoidalis and from the nucleus of the tractus ovoidalis. The AR- nucleus also receives an overlapping, major projection from previously uncharted regions of the medial arcopallium and a minor projection from the caudomedial nidopallium. Both the AR- and the AR+ nuclei project to the intercollicular nucleus of the midbrain. No obvious sex differences in either the pattern of AR immunoreactivity or of the afferent projections to the AR- nucleus were observed. The significance of these results in terms of the acoustic control of avian reproductive behavior is discussed, and a comparison with the organization of VMH afferents in lizards suggests a homologous similarity of the caudal telencephalon in sauropsids.

Dorsal pallidal neurons directly link the nidopallium and midbrain in the zebra finch (Taeniopygia guttata).

The dorsal pallidum in birds is considered similar, if not homologous, to the globus pallidus (GP) of mammals. The dorsal pallidum projects to both thalamic and midbrain targets similar to the direct and indirect pathways arising from the internal and external segments of the GP. In the present study, retrograde and anterograde tracing studies revealed a previously undescribed projection of the avian dorsal pallidum. This arises from a specific dorsomedial component, which terminates in the intercollicular nucleus and partly surrounds the avian equivalent of the central nucleus of the inferior colliculus. The respiratory-vocal dorsomedial nucleus of the intercollicular complex, however, does not receive these projections. The somata of the pallidal neurons retrogradely labeled from injections in the intercollicular nucleus were large and generally multipolar and had extensive, sparsely branching central processes (presumptive dendrites) that together extended up to 2 mm dorsally into the intermediate and caudomedial nidopallium. The size and morphology of these neurons were similar to those of large pallidal neurons labeled by calretinin immunoreactivity, which could be co-localized to the same cells. Thus, rather than being directly involved in the control of movement, the large dorsomedial neurons of the caudal dorsal pallidum may be involved in sensory processing, in that they provide an unusual direct link between sensory (auditory/somatosensory) regions of the nidopallium and sensory regions of the intercollicular nucleus of the midbrain. J. Comp. Neurol. 525:1731-1742, 2017. © 2016 Wiley Periodicals, Inc.

Proposed homology of the dorsomedial subdivision and V-shaped layer of the avian hippocampus to Ammon's horn and dentate gyrus, respectively.

The avian hippocampal formation differs considerably from that of mammals both in terms of position and cytoarchitecture. On the basis of fiber connections in pigeons, however, we previously proposed that the dorsomedial subdivision (DM) and the V-shaped layer of the hippocampal formation correspond to Ammon's horn and the dentate gyrus of mammals, respectively. In the present study, we provide evidence in support of this hypothesis by double staining hippocampal neurons using tract-tracing and gene expression. After cholera toxin subunit B (CTB) was injected into the lateral septal nucleus (SL), and vesicular glutamate transporter 2 (vGluT2) mRNA, a gene marker for glutamatergic neurons, was visualized in the same retrogradely labeled neurons with in situ hybridization, most CTB+/vGluT2+ neurons were concentrated in DM, but were rare in the V-shaped layer. The distribution pattern of CTB+/vGluT2+ neurons in the hippocampal formation did not change when CTB injection sites were shifted in a rostrocaudal direction in SL. SL expresses a variety of mRNAs for ionotropic glutamate receptor subunits (GluA1, GluA2, GluK2, GluK4, and GluN1). The findings indicate that DM neurons provide descending glutamatergic axons to SL. Additionally, the present study showed that Prox1 mRNA, a gene marker for the dentate gyrus in mammals, was intensely expressed in the V-shaped layer in the pigeon hippocampus. Together these results strengthen our original hypothesis that DM and the V-shaped layer in the pigeon hippocampus are homologous to Ammon's Horn and the dentate gyrus, respectively. © 2016 Wiley Periodicals, Inc.

Functional Image-guided Radiotherapy Planning for Normal Lung Avoidance.

For patients with lung cancer undergoing curative intent radiotherapy, functional lung imaging can be incorporated into treatment planning to modify the dose distribution within non-target volume lung by differentiation of lung regions that are functionally defective or viable. This concept of functional image-guided lung avoidance treatment planning has been investigated with several imaging modalities, primarily single photon emission computed tomography (SPECT), but also hyperpolarised gas magnetic resonance (MR) imaging, positron emission tomography (PET) and computed tomography (CT)-based measures of lung biomechanics. Here, we review the application of each of these modalities, review practical issues of lung avoidance implementation, including image registration and the role of both ventilation and perfusion imaging, and provide guidelines for reporting of future lung avoidance planning studies.

A prospective study of pre-trauma risk factors for post-traumatic stress disorder and depression.

BACKGROUND: It is unclear which potentially modifiable risk factors best predict post-trauma psychiatric disorders. We aimed to identify pre-trauma risk factors for post-traumatic stress disorder (PTSD) or major depression (MD) that could be targeted with resilience interventions. METHOD: Newly recruited paramedics (n = 453) were assessed for history of mental disorders with structured clinical interviews within the first week of their paramedic training and completed self-report measures to assess hypothesized predictors. Participants were assessed every 4 months for 2 years to identify any episodes of PTSD and MD; 386 paramedics (85.2%) participated in the follow-up interviews. RESULTS: In all, 32 participants (8.3%) developed an episode of PTSD and 41 (10.6%) an episode of MD during follow-up. In all but nine cases (2.3%), episodes had remitted by the next assessment 4 months later. At 2 years, those with episodes of PTSD or MD during follow-up reported more days off work, poorer sleep, poorer quality of life, greater burn-out; and greater weight-gain for those with PTSD. In line with theories of PTSD and depression, analyses controlling for psychiatric and trauma history identified several pre-trauma predictors (cognitive styles, coping styles and psychological traits). Logistic regressions showed that rumination about memories of stressful events at the start of training uniquely predicted an episode of PTSD. Perceived resilience uniquely predicted an episode of MD. CONCLUSIONS: Participants at risk of developing episodes of PTSD or depression could be identified within the first week of paramedic training. Cognitive predictors of episodes of PTSD and MD are promising targets for resilience interventions.

Interplay between mast cells, enterochromaffin cells, and sensory signaling in the aging human bowel.

BACKGROUND: Advanced age is associated with a reduction in clinical visceral pain perception. However, the underlying mechanisms remain largely unknown. Previous studies have suggested that an abnormal interplay between mast cells, enterochromaffin (EC) cells, and afferent nerves contribute to nociception in gastrointestinal disorders. The aim of this study was to investigate how aging affects afferent sensitivity and neuro-immune association in the human bowel. METHODS: Mechanical and chemical sensitivity of human bowel afferents were examined by ex vivo afferent nerve recordings. Age-related changes in the density of mast cells, EC cells, sensory nerve terminals, and mast cell-nerve micro-anatomical association were investigated by histological and immune staining. KEY RESULTS: Human afferents could be broadly classified into subpopulations displaying mechanical and chemical sensitivity, adaptation, chemo-sensitization, and recruitment. Interestingly human bowel afferent nerve sensitivity was attenuated with age. The density of substance P-immunoreactive (SP-IR) nerve varicosities was also reduced with age. In contrast, the density of ileal and colonic mucosal mast cells was increased with age, as was ileal EC cell number. An increased proportion of mast cells was found in close apposition to SP-IR nerves. CONCLUSIONS & INFERENCES: Afferent sensitivity in human bowel was reduced with advancing age. Augmentation of mast cells and EC cell numbers and the mast cell-nerve association suggest a compensatory mechanism for sensory neurodegeneration.