Delayed timing of breeding attempts, but not time lost to nest construction, reduces the annual reproductive output of the Eastern Phoebe (Sayornis phoebe)

For many birds, nest construction is a costly aspect of parental care, trading finite energetic resources between parental care and self-maintenance. For multi-brooded organisms with short breeding seasons, such as migratory passerines, repeated nest construction could be especially costly if the activity delays the onset of breeding attempts. Earlier studies on passerines that reuse nests between breeding seasons suggested that time lost to initial nest construction reduces seasonal reproductive output. However, costs associated with building new nests between breeding attempts, within the same breeding season, have largely been ignored. Here, we experimentally removed first nests, after fledging or failing, of Eastern Phoebes ( Sayornis phoebe), to evaluate how the annual onset of breeding and nest construction between breeding attempts affected parental investment into second attempts. We found that first egg laying date negatively predicted the probability of second breeding attempts, but experimental treatment (first nest removal vs. control) did not. Neither first egg laying date nor treatment statistically influenced any of the reproductive traits in second breeding attempts (clutch size, nestling body condition, and nestling growth rate). We conclude that in this species, second breeding attempts are limited by the initial onset of seasonal reproduction, and not by time lost to nest construction between breeding attempts.

Case Report: Pulmonary Conidiobolomycosis in a Vietnamese Pot-Bellied Pig

An adult castrated male Vietnamese pot-bellied pig had a 1-week history of acute dyspnea and lethargy. Minimal diagnostic testing was authorized by the owner, resulting in treatment with a third-generation cephalosporin and a non-steroidal anti-inflammatory drug. Partial improvement was observed after a week; however, the pig died 2 weeks after the initial onset of clinical signs. Macroscopically, ~90% of the left lung was effaced by large masses with a caseonecrotic center. Histologic examination revealed eosinophilic granulomas with myriad, intralesional, negatively staining hyphae highlighted by “sleeves” of hypereosinophilic material (Splendore-Hoeppli material). Infection with an oomycete or “zygomycete” (i.e., organisms of the order Entomophthorales or Mucorales) was initially considered. Pan-fungal PCR and sequencing performed on formalin-fixed, paraffin-embedded lung tissue identified Conidiobolus spp., consistent with a diagnosis of primary pulmonary conidiobolomycosis. There are only a few reports of infections with Conidiobolus spp. (and other members of the order Entomophthorales) in swine. Unlike humans and other animal species, conidiobolomycosis in pigs presents more commonly as a primary pulmonary disease rather than rhinofacial or nasopharyngeal disease.

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome of femoral neoplasm-like onset: a case-based review

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is an umbrella term covering a constellation of bone lesions and skin manifestations, but has rarely been clarified in the clinic. We report a 28-year-old woman who had initial onset of SAPHO syndrome with involvement of the femur, and she experienced a tortuous diagnostic course. We also performed a literature review of SAPHO syndrome cases involving the femur and summarize several empirical conclusions by integrating previous findings with our case. Furthermore, we propose our perspective that ailment of the skin caused by infection of pathogens might be the first hit for triggering or perpetuating the activation of the immune system. As a result, musculoskeletal manifestations are probably the second hit by crosstalk of an autoimmune reaction. The skin manifestations preceding bone lesions can be well explained. Current interventions for SAPHO syndrome remain controversial, but drugs aiming at symptom relief could serve as the first preference for treatment. An accurate diagnosis and appropriate treatment can cure patients in a timely manner. Although the pathogenesis of SAPHO syndrome remains to be determined, physicians and surgeons still need to heighten awareness of this entity to avoid invasive procedures, such as frequent biopsies or nonessential ostectomy.

The output of interneurons in the primary visual cortex is best reflected by pre-synaptic activity, not somatic activity

Recent advances in 2-photon calcium-imaging in awake mice have made it possible to study the effect of different behavioural states on cortical circuitry. Many studies assume that somatic activity can be used as a measure for neuronal output. We set out to test the validity of this assumption by comparing somatic activity with the pre-synaptic activity of VIP (Vasoactive intestinal peptide)- and SST (Somatostatin)-positive interneurons in layer 2/3 of the primary visual cortex (V1). We used mice expressing genetically encoded calcium indicators in VIP/SST-interneurons across the whole cell (VIP/SST:GCaMP6f) or confined to pre-synapses (VIP/SST:SyGCaMP5). Mice were exposed to a full-field visual stimulation protocol consisting of 60-second-long presentations of moving Gabor gratings (0.04 cpd, 2 Hz) alternated by 30 seconds of grey screen. During imaging, mice were placed on an air-suspended Styrofoam ball, allowing them to run voluntarily. We compared neural activity during three 4-second time-windows: Before visual stimulation (−4 to 0 sec), during the initial onset (1 to 5 sec) and at the end of the stimulation (56 to 60 sec.). These were further compared while the mice were stationary and while they were voluntarily locomoting. Unlike VIP-somas, VIP-pre-synapses showed strong suppressive responses to the visual stimulus. Furthermore, VIP-somas were positively correlated with locomotion, whereas in VIP-synapses we observed a split between positive and negative correlations. In addition, a similar but weaker distinction was found between SST-somas and pre-synapses. The excitatory effect of locomotion in VIP-somas increased over the course of the visual stimulus but this property was only shared with the positively correlated VIP-pre-synapses. The remaining negatively correlated pre-synapses showed no relation to the overall activity of the Soma. Our results suggest that when making statements about the involvement of interneurons in V1 layer 2/3 circuitry it is crucial to measure from synaptic terminals as well as from somas.

New Perspectives on the Immunopathogenesis and Treatment of Uveitis Associated With Vogt-Koyanagi-Harada Disease

Uveitis associated with Vogt-Koyanagi-Harada (VKH) disease is a bilateral, chronic, granulomatous autoimmune disease associated with vitiligo, poliosis, alopecia, and meningeal and auditory manifestations. The disease affects pigmented races with a predisposing genetic background. Evidence has been provided that the clinical manifestations are caused by a T-lymphocyte-mediated autoimmune response directed against antigens associated with melanocytes in the target organs. Alongside of T lymphocytes, autoreactive B cells play a central role in the development and propagation of several autoimmune diseases. The potential role of B lymphocytes in the pathogenesis of granulomatous uveitis associated with VKH disease is exemplified within several studies. The early initial-onset acute uveitic phase typically exhibits granulomatous choroiditis with secondary exudative retinal detachment and optic disc hyperemia and swelling, subsequently involving the anterior segment if not adequately treated. The disease eventually progresses to chronic recurrent granulomatous anterior uveitis with progressive posterior segment depigmentation resulting in “sunset glow fundus” appearance and chorioretinal atrophy if not properly controlled. Chronically evolving disease is more refractory to treatment and, consequently, vision-threatening complications have been recognized to occur in the chronic recurrent phase of the disease. Conventional treatment with early high-dose systemic corticosteroids is not sufficient to prevent chronic evolution. Addition of immunomodulatory therapy with mycophenolate mofetil as first-line therapy combined with systemic corticosteroids in patients with acute initial-onset disease prevents progression to chronic evolution, late complications, vitiligo, and poliosis. Furthermore, patients under such combined therapy were able to discontinue treatment without relapse of inflammation. These findings suggest that there is a therapeutic window of opportunity for highly successful treatment during the early initial-onset acute uveitic phases, likely because the underlying disease process is not fully matured. It is hypothesized that early and aggressive immunosuppressive therapy will prevent remnant epitope generation in the initiation of the autoimmune process, the so-called primary response. B cell depleting therapy with the anti-CD20 monoclonal antibody rituximab is effective in patients with refractory chronic recurrent granulomatous uveitis. The good response after rituximab therapy reinforces the idea of an important role of B cells in the pathogenesis or progression of chronic recurrent uveitis associated with VKH disease.

Constipation and Syncope

A 43-year-old woman sought care for severe constipation associated with syncopal episodes. Her constipation alternated with explosive diarrhea. Chronic left-sided abdominal pain and severe bloating developed after eating. She was diagnosed with irritable bowel syndrome. After the initial onset of symptoms, nausea, bloating, and intractable vomiting developed. Symptoms were exacerbated by food and were partially relieved with vomiting. She had multiple episodes of bilious, undigested emesis per day. Trials of antiemetics and motility agents provided no substantial relief. She adopted a liquid diet, avoided solid foods, and eventually had a gastrostomy tube placed. She lost at least 15.9 kg over 2 years. Review of systems was significant for generalized fatigue and a burning sensation in her hands and feet. Her medical history was pertinent for Graves disease previously treated with remote thyroid radioablation, and she was now taking thyroid hormone replacement therapy. Neurologic examination findings were normal except for unreactive pupillary light reflexes. A gastrointestinal tract transit study showed persistently delayed colonic transit with mildly delayed gastric emptying. Autonomic reflex screening showed diffuse postganglionic sympathetic sudomotor, severe cardiovagal, and severe cardiovascular adrenergic impairment. Thermoregulatory sweat testing showed diffuse anhidrosis. Creatinine value was mildly increased. The serum was strongly positive for ganglionic (alpha 3) acetylcholine receptor-immunoglobulin G. The findings strongly suggested an autonomic autoimmune polyganglionopathy, with autoimmune gastrointestinal dysmotility as the predominant phenotype. She received intravenous immunoglobulin. She had complete resolution of her previous constipation, nausea, and vomiting. She regained 22.7 kg. Her gastrostomy tube was removed. Repeated gastrointestinal tract transit studies approached normal findings. Repeated autonomic testing and thermoregulatory sweat testing showed improvement. Over several months, the intravenous immunoglobulin dose was tapered. The patient remained asymptomatic for 8 years on long-term immunosuppression with azathioprine, she had a recurrence of her previous symptoms. Repeated gastrointestinal tract transit studies again showed delayed gastrointestinal tract emptying. Another intravenous immunoglobulin course controlled her symptoms, with normalization of gastrointestinal tract transit studies. Autoimmune gastrointestinal dysmotility can manifest as either hypomotility or hypermotility but most often presents as gastroparesis or pseudo-obstruction. Symptoms include nausea, vomiting, bloating, early satiety, diarrhea, constipation, and involuntary weight loss. It can be idiopathic or paraneoplastic. Risk factors for idiopathic cases include personal or family histories of autoimmunity.

Seizures 3 Months After Endarterectomy

A 57-year-old woman had development of acute-onset, right-sided weakness and sensory change (face, arm, and leg) when at a casino. She was brought to the emergency department, and her symptoms had essentially resolved upon her arrival. Brain magnetic resonance imaging showed no acute stroke, and a transient ischemic attack was diagnosed. She was transferred to an academic medical center. Investigations showed high-grade left internal carotid artery stenosis; the same day, a stent was placed via endovascular procedure by an interventional neuroradiologist. Magnetic resonance imaging of the head showed an enhancing lesion with surrounding edema in the left frontal and parietal lobes at the cortex, also involving the nearby leptomeninges. Electroencephalography showed potentially epileptogenic discharges over the left central head region. Brain biopsy was performed, which showed abundant CD68+ macrophages, granulomatous inflammation, and necrosis associated with foreign material. The associated lymphocytic infiltrates were predominantly composed of CD3+ T cells and only sparse CD20+ B cells. The foreign material seen was lamellated, amorphous, nonpolarizable, and nonrefractile, typical of hydrophilic polymers commonly used in intravascular medical devices. The patient was diagnosed with seizures caused by multifocal, intracranial, foreign-body, granulomatous reaction to polymers that had embolized to brain parenchyma during the prior endovascular procedure. To suppress this inflammatory reaction, corticosteroids were initiated—intravenous methylprednisolone, followed by an oral prednisone course, with a plan to gradually taper. Antiseizure medication was continued at the same doses. The patient’s seizures remitted initially but relapsed upon corticosteroid dose reduction despite a very slow prednisone taper. At that point, 18 months after the initial onset of seizures, the patient had cushingoid features, depression, and chronic insomnia. During the next year, 2 steroid-sparing strategies were employed sequentially. In patients who have received neurovascular medical device therapy and have subsequent development of seizures, focal neurologic deficit, headache, or encephalopathy, central nervous system inflammation triggered by retained foreign-body material should be considered as a potential cause.

The Acquisition of Acoustic Cues to Onset and Coda Voicing Contrasts by Preschoolers With Hearing Loss

Purpose Children with hearing loss (HL), including those with hearing aids (HAs) and cochlear implants (CIs), often have difficulties contrasting words like “ b each ” versus “ p each ” and “ do g ” versus “ do ck ” due to challenges producing systematic voicing contrasts. Even when acoustic contrasts are present, these may not be perceived as such by others. This can cause miscommunication, leading to poor self-esteem and social isolation. Acoustic evidence is therefore needed to determine if these children have established distinct voicing categories before entering school and if misperceptions are due to a lack of phonological representations or due to a still-maturing implementation system. The findings should help inform more effective early intervention. Method Participants included 14 children with HL (eight HA users, five CI users, and one bimodal) and 20 with normal hearing, all English-speaking preschoolers. In an elicited imitation task, they produced consonant–vowel–consonant minimal pair words that contrasted voicing in word-initial (onset) or word-final (coda) position at all three places of articulation (PoAs). Results Overall, children with HL showed acoustically distinct voicing categories for both onsets and codas at all three PoAs. Contrasts were less systematic for codas than for onsets, as also confirmed by adults' perceptual ratings. Conclusions Preschoolers with HL produce acoustic differences for voiced versus voiceless onsets and codas, indicating distinct phonological representations for both. Nonetheless, codas were less accurately perceived by adult raters, especially when produced by CI users. This suggests a protracted development of the phonetic implementation of codas, where CI users, in particular, may benefit from targeted intervention.

Serum Interleukin-15 in Alopecia Areata and its correlation with dermoscopic findings

Background Alopecia areata is an autoimmune hair loss which frequently starts in childhood. Its presentation had an extreme variability not only in the time of initial onset but also in the duration, extent, and pattern of hair loss during any given episode of active loss. Moreover, the course of disease is unpredictable, with spontaneous regrowth of hair occurring in 80% of patients within the first year and sudden relapse at any given time. Due to the clinical variability and unpredictable nature of spontaneous regrowth, diagnosis and management may be difficult and challenging. Objective The aim of this study is to evaluate the serum levels of IL-15 in active alopecia areata and correlate them with disease severity and activity according to dermoscopic findings. Methods This case-control study were conducted in Dermatology, Venereology and Andrology department, Ain Shams University Hospitals included 30 patients with different clinical variants of AA, the diagnosis was made via clinical examination and dermoscopic findings. In addition, 30 apparently healthy individuals of matched age and sex as a control group were included in the study. Results Dermoscopic examination among cases showed that the most common dermoscopic findings in patients were vellus hair and yellow dots, while the least common finding was exclamation mark hairs. On comparing serum IL-15 in patients and control groups, it was found that serum levels of IL-15 in patients were significantly higher than those in the control group. There was no statistically significant difference in serum IL-15 levels between patients with negative and positive pull test, nail involvement, or body involvement. Similarly, no statistically significant difference in serum IL-15 levels in patients with various subjective disease activity was detected. However, there was a highly significant difference between serum IL-15 levels in different SALT score groups, with the highest levels being in the S3 group. There was a highly significant difference between IL-15 levels in patients with and without black dots. Also, there was significant difference between IL-15 in patients with and without broken hair, and exclamation mark hair. There was no significant difference in level of IL-15 among patients with and without yellow dots, and with and without vellus hair. Conclusion On the basis of the current study, we can conclude that IL-15 is significantly elevated in AA patients when compared to the control subjects. It is also a possible marker of AA severity. It is positively correlated with dermoscopic findings in AA patients, so dermoscopic findings can be useful in evaluating severity of alopecia areata.