Secondary hypogammaglobulinemia (SHG) is characterized by reduced immunoglobulin levels due to acquired causes of decreased antibody production or increased antibody loss. Clarification regarding ...whether the hypogammaglobulinemia is secondary or primary is important because this has implications for evaluation and management. Prior receipt of immunosuppressive medications and/or presence of conditions associated with SHG development, including protein loss syndromes, are histories that raise suspicion for SHG. In patients with these histories, a thorough investigation of potential etiologies of SHG reviewed in this report is needed to devise an effective treatment plan focused on removal of iatrogenic causes (eg, discontinuation of an offending drug) or treatment of the underlying condition (eg, management of nephrotic syndrome). When iatrogenic causes cannot be removed or underlying conditions cannot be reversed, therapeutic options are not clearly delineated but include heightened monitoring for clinical infections, supportive antimicrobials, and in some cases, immunoglobulin replacement therapy. This report serves to summarize the existing literature regarding immunosuppressive medications and populations (autoimmune, neurologic, hematologic/oncologic, pulmonary, posttransplant, protein-losing) associated with SHG and highlights key areas for future investigation.
Burning mouth syndrome (BMS) is a debilitating, idiopathic chronic pain condition. For many BMS patients, burning oral pain begins in late morning and becomes more intense throughout the day, peaking ...by late afternoon or evening. We investigated brain gray matter volume (GMV) with voxel-based morphometry (VBM), white matter fractional anisotropy (FA) with diffusion tensor imaging (DTI), and functional connectivity in resting state functional MRI (rsfMRI) in a tightly screened, homogeneous sample of 9 female, postmenopausal/perimenopausal BMS patients and 9 matched healthy control subjects. Patients underwent 2 scanning sessions in the same day: in the morning, when ongoing pain/burning was low, and in the afternoon, when pain/burning was significantly higher. Patients had increased GMV and lower FA in the hippocampus (Hc), and decreased GMV in the medial prefrontal cortex (mPFC). rsfMRI revealed altered connectivity patterns in different states of pain/burning, with increased connectivity between mPFC (a node in the default mode network) and anterior cingulate cortex, occipital cortex, ventromedial PFC, and bilateral Hc/amygdala in the afternoon compared with the morning session. Furthermore, mPFC-Hc connectivity was higher in BMS patients than control subjects for the afternoon but not the morning session. mPFC-Hc connectivity was related to Beck depression inventory scores both between groups and between burning states within patients, suggesting that depression and anxiety partially explain pain-related brain dysfunction in BMS. Overall, we provide multiple lines of evidence supporting aberrant structure and function in the mPFC and Hc, and implicate a circuit involving the mPFC and Hc in regulating mood and depressive symptoms in BMS.
Lipid droplets (LDs) provide a reservoir for triacylglycerol storage and are a central hub for fatty acid trafficking and signaling in cells. Lipolysis promotes mitochondrial biogenesis and oxidative ...metabolism via a SIRT1/PGC-1α/PPARα-dependent pathway through an unknown mechanism. Herein, we identify that monounsaturated fatty acids (MUFAs) allosterically activate SIRT1 toward select peptide-substrates such as PGC-1α. MUFAs enhance PGC-1α/PPARα signaling and promote oxidative metabolism in cells and animal models in a SIRT1-dependent manner. Moreover, we characterize the LD protein perilipin 5 (PLIN5), which is known to enhance mitochondrial biogenesis and function, to be a fatty-acid-binding protein that preferentially binds LD-derived monounsaturated fatty acids and traffics them to the nucleus following cAMP/PKA-mediated lipolytic stimulation. Thus, these studies identify the first-known endogenous allosteric modulators of SIRT1 and characterize a LD-nuclear signaling axis that underlies the known metabolic benefits of MUFAs and PLIN5.
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•MUFAs allosterically activate SIRT1 toward select substrates such as PGC-1α•MUFAs enhance PGC-1α signaling in vivo in a SIRT1-dependent manner•PLIN5 is a fatty acid binding protein that preferentially binds LD-derived MUFAs•PLIN5 mediates MUFA signaling to control SIRT1/PGC-1α
Najt et al. identify the first-known endogenous allosteric modulator of SIRT1 and characterize a lipid droplet-nuclear signaling axis that underlies the known metabolic benefits of monounsaturated fatty acids and PLIN5.
•Parabrachial-periaqueductal gray FC correlates with subsequent pain.•Subgenual anterior cingulate cortex-PAG FC correlates with tonic pain.•PAG- and amydalocortical networks at rest correlate with ...subsequent tonic pain.•Cortical FC of PAG supports additional targets of neuromodulation to control pain.
Resting state functional connectivity (FC) is widely used to assess functional brain alterations in patients with chronic pain. However, reports of FC accompanying tonic pain in pain-free persons are rare. A network we term the Descending Pain Modulatory Network (DPMN) is implicated in healthy and pathologic pain modulation. Here, we evaluate the effect of tonic pain on FC of specific nodes of this network: anterior cingulate cortex (ACC), amygdala (AMYG), periaqueductal gray (PAG), and parabrachial nuclei (PBN).
In 50 pain-free participants (30F), we induced tonic pain using a capsaicin-heat pain model. functional MRI measured resting BOLD signal during pain-free rest with a 32 °C thermode and then tonic pain where participants experienced a previously warm temperature combined with capsaicin. We evaluated FC from ACC, AMYG, PAG, and PBN with correlation of self-report pain intensity during both states. We hypothesized tonic pain would diminish FC dyads within the DPMN.
Of all hypothesized FC dyads, only PAG and subgenual ACC was weakly altered during pain (F = 3.34; p = 0.074; pain-free>pain d = 0.25). After pain induction sACC-PAG FC became positively correlated with pain intensity (R = 0.38; t = 2.81; p = 0.007). Right PBN-PAG FC during pain-free rest positively correlated with subsequently experienced pain (R = 0.44; t = 3.43; p = 0.001). During pain, this connection's FC was diminished (paired t=-3.17; p = 0.0026). In whole-brain analyses, during pain-free rest, FC between left AMYG and right superior parietal lobule and caudate nucleus were positively correlated with subsequent pain. During pain, FC between left AMYG and right inferior temporal gyrus negatively correlated with pain. Subsequent pain positively correlated with right AMYG FC with right claustrum; right primary visual cortex and right temporo-occipitoparietal junction
We demonstrate sACC-PAG tonic pain FC positively correlates with experienced pain and resting right PBN-PAG FC correlates with subsequent pain and is diminished during tonic pain. Finally, we reveal PAG- and right AMYG-anchored networks which correlate with subsequently experienced pain intensity. Our findings suggest specific connectivity patterns within the DPMN at rest are associated with subsequently experienced pain and modulated by tonic pain. These nodes and their functional modulation may reveal new therapeutic targets for neuromodulation or biomarkers to guide interventions.
Allergic contact dermatitis to metals has become increasingly recognized in patients with endovascular implants. The ACD can lead to in-stent restenosis as well as a prominent eczematous reaction ...overlying the implant, often necessitating its removal. We present a case of refractory allergic contact dermatitis to nickel in a 44-year-old man with numerous endovascular stents and vascular clips. He developed numerous adverse effects of systemic therapy to manage his symptoms including recurrent infections leading to frequent hospitalizations. He was effectively transitioned to dupilumab, a monoclonal antibody against the IL-4α subunit currently approved by the Food and Drug Administration in the management of atopic dermatitis, with an improvement in symptoms and a reduction in infection rate.
Statins are widely used to inhibit cholesterol production in the liver among people with hypercholesterolemia. A recent epidemiological study in the UK has shown that statin use (unlike elevated BMI) ...is not associated with an increased risk of Achilles tendon rupture. However, because of laboratory reports suggesting a negative influence of statins on tenocyte metabolism, we decided to directly compare the Achilles tendon structure (cross-sectional area and longitudinal collagen organization) in regular statin users compared to non-users.
We conducted ultrasound tissue characterization (UTC) of the Achilles tendon in statin users and a comparison group of similar age and gender. Statin users and control participants were recruited from May 10 2015 to February 17 2017 through a cardiovascular health centre and from the general community. Cross-sectional area of the Achilles tendon and longitudinal collagen organization (% type I echoes) were assessed using quantitative ultrasound tissue characterization by a blinded observer at a predetermined location (2 cm proximal to the calcaneus).
Sixty-six individuals who were either taking statins for at least one year (ST, n = 33) or a comparison group who had never taken statins (CG, n = 33) were included in the study. The Achilles tendon cross-sectional area (ST 59.7 (13) mm2, CG 59.9 (8.5) mm2) and proportion of echo-type I patterns ST 70 (10)%, CG 74 (13)% were equivalent in the two groups. In contrast, there was a negative correlation between BMI (rs = -0.25, p = 0.042) and type I echo values. Obese individuals demonstrated a significantly lower percentage of type I echoes (62 (11)%) than individuals of normal body mass index (73 (10)% p<0.05).
These findings demonstrate that there is no evidence of a negative statin influence on Achilles tendon structure. Given earlier reports that the risk of Achilles injury is equivalent in statin users and non-users, weightbearing exercise may be prescribed without placing the Achilles tendon at a higher risk of injury than among the general population. The results of this study are consistent with the known negative effects of elevated BMI on tendon structure, suggesting that an assessment of the Achilles tendons prior to prescribing weightbearing exercise may be prudent in obese individuals.
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