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Purpose: High-quality, comprehensive care of vulnerable populations requires interprofessional ambulatory care teams skilled in addressing complex social, medical, and psychological needs. Training health professionals in interprofessional settings is crucial for building a competent future workforce. The impacts on care utilization of adding continuity trainees to ambulatory teams serving vulnerable populations have not been described. We aim to understand how the addition of interprofessional trainees to an ambulatory clinic caring for Veterans experiencing homelessness impacts medical and mental health services utilization., Methods: Trainees from five professions were incorporated into an interprofessional ambulatory clinic for Veterans experiencing homelessness starting in July 2016. We performed clinic-level interrupted time series (ITS) analyses of pre- and post-intervention utilization measures among patients enrolled in this training continuity clinic, compared to three similar VA homeless clinics without training programs from October 2015 to September 2018., Results: Our sample consisted of 37,671 patient- months. There was no significant difference between the intervention and comparison groups' post-intervention slopes for numbers of primary care visits (difference in slopes =-0.16 visits/100 patients/month; 95% CI -0.40, 0.08; p=0.19), emergency department visits (difference in slopes = 0.08 visits/100 patients/month; 95% CI -0.16, 0.32; p=0.50), mental health visits (difference in slopes = -1.37 visits/month; 95% CI -2.95, 0.20; p= 0.09), and psychiatric hospitalizations (-0.005 admissions/100 patients/month; 95% CI -0.02, 0.01; p= 0.62). We found a clinically insignificant change in medical hospitalizations., Conclusions: Adding continuity trainees from five health professions to an interprofessional ambulatory clinic caring for Veterans experiencing homelessness did not adversely impact inpatient and outpatient care utilization. An organized team-based care approach is beneficial for vulnerable patients and provides a meaningful educational experience for interprofessional trainees by building health professionals' capabilities to care for vulnerable populations., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Pannexins constitute a family of three glycoproteins (Panx1, -2, and -3) forming single membrane channels. Recent work demonstrated that Panx1 is expressed in skeletal muscle and involved in the potentiation of contraction. However, Panxs functions in skeletal muscle cell differentiation, and proliferation had yet to be assessed. We show here that Panx1 and Panx3, but not Panx2, are present in human and rodent skeletal muscle, and their various species are differentially expressed in fetal versus adult human skeletal muscle tissue. Panx1 levels were very low in undifferentiated human primary skeletal muscle cells and myoblasts (HSMM) but increased drastically during differentiation and became the main Panx expressed in differentiated cells. Using HSMM, we found that Panx1 expression promotes this process, whereas it was impaired in the presence of probenecid or carbenoxolone. As for Panx3, its lower molecular weight species were prominent in adult skeletal muscle but very low in the fetal tissue and in undifferentiated skeletal muscle cells and myoblasts. Its overexpression (∼43-kDa species) induced HSMM differentiation and also inhibited their proliferation. On the other hand, a ∼70-kDa immunoreactive species of Panx3, likely glycosylated, sialylated, and phosphorylated, was highly expressed in proliferative myoblasts but strikingly down-regulated during their differentiation. Reduction of its endogenous expression using two Panx3 shRNAs significantly inhibited HSMM proliferation without triggering their differentiation. In summary, our results demonstrate that Panx1 and Panx3 are co-expressed in human skeletal muscle myoblasts and play a pivotal role in dictating the proliferation and differentiation status of these cells., (© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.)

A 41-year-old woman previously diagnosed with generalized eruptive keratoacanthomas of Grzybowski type presented with bilateral lower eyelid cicatrical ectropions. She had previously undergone multiple resections of syringomatous adenomas of both nipples, facial keratoacanthomas, and a lower left lip squamous cell carcinoma. Her facial and periocular skin was thickened with a cobblestone appearance. Cicatricial ectropions involved both upper and lower eyelids. Donor skin was harvested from the dorsum of the foot as this was the only disease-free area on her body, and she achieved a stable result with reduced tearing and improved appearance.

Having shown that Panx1 and Panx3 are expressed in the epidermis, we investigated their distribution in human skin adnexal structures and skin cancer. Both proteins were found in hair follicles, sebaceous and eccrine glands, as well as blood vessels. Panx1 was detected as punctate or diffuse intracellular labeling, while Panx3 was only observed as diffuse intracellular staining, suggesting different functions. We also identified the Panx3 immunoreactive ~70 kD species modulated during keratinocyte differentiation as Panx3. Since our data indicate that pannexins are regulated during keratinocyte differentiation, we assessed whether their levels are altered under circumstances in which keratinocyte differentiation is compromised. We found that Panx1 and Panx3 levels are highly reduced in human keratinocyte tumors, thus showing for the first time that both pannexins are dysregulated in human cancers. Altogether, these data suggest that Panx1 and Panx3 have distinct and unique functions within the skin in health and disease.

Connexin43 (Cx43) is known to have tumor-suppressive effects, but the underlying mechanisms are still poorly understood. In keratinocytes, we previously showed that the COOH-terminal domain of Cx43 directly interacts with the tumor suppressor Cav-1. We now show that rat epidermal keratinocytes (REK) that are reduced in Cx43 present features of epithelial-to-mesenchymal transition and are more invasive than their control counterparts, whereas overexpression of Cx43 inhibited the 12-O-tetradecanoyl-phorbol-13-acetate (TPA)- and epidermal growth factor (EGF)-induced invasive properties. Carbenoxolone did not alter the inhibitory effect of Cx43 against TPA- and EGF-induced cell invasion, indicating the involvement of a gap junctional intercellular communication-independent mechanism. Interestingly, the association of Cx43 with Cav-1 was found to be reduced after TPA and EGF treatment. Accordingly, the colocalization of Cx43 with Cav-1 was diminished in cells from a human epidermal squamous cell carcinoma, as well as in sections from human keratinocyte tumors, suggesting that Cx43/Cav-1 interaction plays a protective role against keratinocyte transformation. As opposed to cells that overexpress Cx43-GFP, invasion could be induced in rat epidermal keratinocytes that overexpressed a GFP-tagged truncated mutant of Cx43 (Delta244-GFP) that we previously showed not to interact with Cav-1, as well as in cells that overexpressed Cx43-GFP but were reduced in Cav-1. Our data show that Cx43 possesses tumor-suppressive properties in keratinocytes and provide the first evidence that the Cx43/Cav-1 interaction is altered in keratinocyte transformation processes, as well as in human keratinocyte tumors, and that this association might play a role in Cx43-mediated tumor suppression., ((c)2010 AACR.)

Unlabelled: Periocular haemangioma of childhood can severely impact visual development., Objective(s): To review our experience with 20 periocular haemangioma patients; to review infant ocular development in the context of periocular capillary haemangioma; to identify early clinical warning signs that may precede devastating visual outcomes in the absence of timely management and to review our experience with surgical debulking for the treatment of selected periocular haemangioma., Design: Retrospective case series., Interventions: Twenty children with congenital periocular haemangiomas received care by a multidisciplinary team consisting of doctors from the specialties ophthalmology, plastic surgery, paediatrics and dermatology. The patients were separated by age at presentation to our centre (1 year). Based on consensus amongst the team, certain patients were considered to be at high risk for development of amblyopia, permanent cortical visual change or blindness. These patients were scheduled for urgent surgical excision or debulking. The effect of treatment on visual development over time was evaluated., Results: Patients presenting to our centre after 1 year of age were more likely to have amblyopia (75% vs. 0% if presenting at

Background: Thrombosis, mucinosis and necrosis are well-described complications of subcutaneous interferon beta injections., Methods: We report 12 incisional biopsies from subcutaneous interferon beta injection sites in 12 multiple sclerosis (MS) patients from a single neurologist's practice., Results: We identified abscesses (two cases) or induration (two cases) in acute clinical lesions and lipoatrophy (eight cases) in chronic lesions (biopsied over a year after symptom onset at injection sites). Biopsies from three acute lesions showed vascular thrombosis, dermal mucinosis, lobular neutrophilic panniculitis, necrosis, calcification and hemosiderin deposition (biopsied 2 weeks to 2 months after symptom onset). Two cases contained sterile abscesses. Five of the eight chronic cases presented as hard, indurated lipoatrophy with livedo reticularis. Their biopsies showed subcutaneous calcification and lipoatrophy. Biopsies from the early calcific suppurative and late calcific atrophic phases histologically resembled the early and late phases of subcutaneous saponification in pancreatic panniculitis., Conclusions: Reactions at the site of subcutaneous interferon beta injections are common. Lipoatrophy can be clinically identified in 39 of 85 MS patients (46%) receiving subcutaneous interferon beta injections for 1 year or longer in our practice. A reaction to interferon should be considered in the differential diagnosis of biopsies that show features of pancreatic panniculitis.

Our aim was to find out if a modified intravenous regional anaesthetic block technique, used for invasive surgical procedures on the distal forearm and hand, results in a drier operative field than traditional methods. Twenty consenting adult (age > 18) patients who were to have an operation on the distal forearm or hand were randomised into two groups (n=10 in each). The first group was using a traditional bier block, with a double upper arm tourniquet. The second group was using a modified regional anaesthetic block technique, with a single upper arm tourniquet, and a single forearm tourniquet. All operative fields were recorded photographically and judged by the operating surgeon as "wet" or "dry". Analgesic requirements and subjective pain were recorded. Plasma lignocaine concentrations were measured. "Wet" operative fields were seen in 6 of the conventional and 0 of the modified group (p=0.01). Patients in the modified group were more comfortable during the procedures (p=0.004). This benefit was not sustained postoperatively (p=0.57). Plasma lignocaine concentrations were higher in the conventional group (p=0.004). The modified technique was as safe as the conventional technique but has the benefits of a drier surgical field and improved intraoperative comfort for patients.

Lipoatrophy and localized panniculitis have been described as rare complications of daily subcutaneous glatiramer acetate injections for the treatment of relapsing-remitting multiple sclerosis (MS). We describe the biopsies from two MS patients in a single neurologist's practice who developed clinical lesions of lipoatrophy at the sites of subcutaneous glatiramer acetate injections. These biopsies showed a lobular panniculitis with lipoatrophy that more closely resembled lupus panniculitis than previous reports of localized panniculitis at glatiramer acetate injection sites. In one case, the area of clinical lipoatrophy continued to enlarge for 6 months after stopping glatiramer acetate therapy, before stabilizing at its current size for the last 8 months. Injection site reactions to glatiramer acetate should be considered in the differential diagnosis of biopsies that show a lupus panniculitis-like appearance. Our observations indicate that glatiramer acetate induced panniculitis is common and may continue to progress after therapy has stopped. In this single neurologist's practice, 64% of the patients receiving daily glatiramer acetate injections had clinical evidence of lipoatrophy or panniculitis. Of 100 consecutive patients receiving therapy for MS between February and November 2006, 14 patients were on glatiramer acetate, 9 of whom had clinical lipoatrophy.

Connexin43 (Cx43) has been reported to interact with caveolin (Cav)-1, but the role of this association and whether other members of the caveolin family bind Cx43 had yet to be established. In this study, we show that Cx43 coimmunoprecipitates and colocalizes with Cav-1 and Cav-2 in rat epidermal keratinocytes. The colocalization of Cx43 with Cav-1 was confirmed in keratinocytes from human epidermis in vivo. Our mutation and Far Western analyses revealed that the C-terminal tail of Cx43 is required for its association with Cavs and that the Cx43/Cav-1 interaction is direct. Our results indicate that newly synthesized Cx43 interacts with Cavs in the Golgi apparatus and that the Cx43/Cavs complex also exists at the plasma membrane in lipid rafts. Using overexpression and small interfering RNA approaches, we demonstrated that caveolins regulate gap junctional intercellular communication (GJIC) and that the presence of Cx43 in lipid raft domains may contribute to the mechanism modulating GJIC. Our results suggest that the Cx43/Cavs association occurs during exocytic transport, and they clearly indicate that caveolin regulates GJIC.

Pannexins are mammalian orthologs of the invertebrate gap junction proteins innexins and thus have been proposed to play a role in gap junctional intercellular communication. Localization of exogenously expressed pannexin 1 (Panx1) and pannexin 3 (Panx3), together with pharmacological studies, revealed a cell surface distribution profile and life cycle dynamics that were distinct from connexin 43 (Cx43, encoded by Gja1). Furthermore, N-glycosidase treatment showed that both Panx1 (approximately 41-48 kD species) and Panx3 (approximately 43 kD) were glycosylated, whereas N-linked glycosylation-defective mutants exhibited a decreased ability to be transported to the cell surface. Tissue surveys revealed the expression of Panx1 in several murine tissues--including in cartilage, skin, spleen and brain--whereas Panx3 expression was prevalent in skin and cartilage with a second higher-molecular-weight species present in a broad range of tissues. Tissue-specific localization patterns of Panx1 and Panx3 ranging from distinct cell surface clusters to intracellular profiles were revealed by immunostaining of skin and spleen sections. Finally, functional assays in cultured cells transiently expressing Panx1 and Panx3 were incapable of forming intercellular channels, but assembled into functional cell surface channels. Collectively, these studies show that Panx1 and Panx3 have many characteristics that are distinct from Cx43 and that these proteins probably play an important biological role as single membrane channels.

As forelimb regeneration in Xenopus laevis is mainly a cell proliferative event which results in a spike-shaped appendage, we set out to examine the possibility that insulin is a growth-promoting factor in this process. The objectives were 1) to detect the presence of insulin receptors (IRs) in the liver (a specific target organ for insulin) and IRs in the forelimb regenerates of X. laevis, 2) to determine whether the receptor is similar to IRs identified in other organisms, and 3) to absorb insulin locally by implanting anti-insulin antibody-soaked hydrolyzed polyacrylamide beads into regenerating forelimb outgrowths in order to assess the effects of insulin deprivation on regeneration. The results show that IRs are present in Xenopus liver plasma membranes (XLPM) as well as in plasma membranes of 21 day forelimb regenerates. Insulin binding to this receptor is time-dependent and specific, as unlabeled bovine insulin competes with radioiodinated insulin for binding to XLPM more effectively than insulin-like growth factor-I, guinea pig insulin, or glucagon. Scatchard analysis of insulin binding to XLPM describes a two binding site receptor possessing a low affinity (0.16 nM-1), high capacity (3.2 +/- 0.9 pM/mg) binding site and a high affinity (2.7 nM-1), low capacity (0.5 +/- 0.3 pM/mg) binding site. The holoreceptor has a molecular mass of 380 kDa. The reduced receptor has subunits of 130 kDa and 95 kDa. The 95 kDa subunit undergoes autophosphorylation following insulin stimulation. Implantation of hydrolyzed polyacrylamide beads, saturated with anti-insulin antibody, into regenerating Xenopus forelimbs significantly impeded development of the regenerates and, therefore, demonstrates that insulin is required for growth of Xenopus forelimb regenerates.

The current study was designed to determine if insulin, glucagon and somatostatin-containing cells are present in the pancreas of adult Xenopus laevis. Localization methods utilized included cytochemical aldehyde fuchsin (AF) staining as well as the immunochemical peroxidase antiperoxidase (PAP) procedure for light microscopy. The results show numerous large clusters of AF-positive cells within a network of highly vascularized acinar tissue. PAP immunochemical localization with insulin antibody on adjacent sections demonstrates positive immunoreactivity to AF-positive cell groups and also the presence of immunoreactive insulin (IRI). Cells exhibiting this immunoreactivity are located in the central region of the islet-like structures. Serial sections not only show PAP immunoreactivity for IRI, but also for immunoreactive glucagon (IRG) and immunoreactive somatostatin (IRS) in the same islet-like structure. IRG and IRS-containing cells are situated around the periphery of the islet-like structures, surrounding the central core of IRI-containing cells. Antibody specificity was confirmed by homologous and heterologous antigen immuno-absorbance assays, as well as incubation of adjacent sections in preimmune sera. Based on this data we conclude that: the distribution of cells of the endocrine pancreas of metamorphosed Xenopus laevis is similar to that of many mammals and certain urodeles. Given the apparent specificity of the antigen-antibody reactions, it appears that Xenopus insulin, glucagon and somatostatin are structurally conserved.