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Palmo-plantar lesions in discoid lupus erythematosus (DLE) can be considered a very distinct rarity, generally refractory to conventional treatments. We present a 47-year-old African female patient with a 6-month clinical history of palm and soles erosions. Clinical examination revealed painful multiple, well defined, erosions with an erythematous and scaly central area and peripherical post-inflammatory hyperchromic border bilaterally distributed on the palmo-plantar surfaces. Pterygium inversum unguis involved all nails of both hands. Histological analysis and direct immunofluorescence study confirmed palmo-plantar DLE. Therapy with mycophenolate mofetil (MMF) was initiated with a progressive clearing of palmo-plantar lesions and a drastic reduction of pain. Therapy was well tolerated, neither side effects nor altered laboratory investigations were observed. Our case and literature review confirm that MMF may be an effective approach for the management of refractory palmo-plantar DLE with a safer profile than Azathioprine regarding adverse effects and cutaneous malignancies risk., (© 2021 Wiley Periodicals LLC.)

Colorectal cancer (CRC) is a high incidence cancer and major cause of cancer mortality. Though disease-causing tumor suppressors for major syndromes are well characterized, about 10% of CRC is familial but without mutations in known tumor suppressors. We exhaustively screened 100 polyposis families for APC germline mutations and identified 13, which are APC mutation-negative, microsatellite-stable (MSS), and with undetectable mutation in known tumor suppressors. Whole exome sequencing in three probands uncovered two with germline frameshift NR0B2 mutations, c.293_301delTTGGGTTGGinsAC and c.227delT. Sanger Sequencing identified a third proband with NR0B2 c.157_166delCATCGCACCT frameshift mutation. All three mutations deleted the C-terminus activation/repression domain of NR0B2, thus are loss-of-function mutations. Real-time RT-PCR performed on tumor and matched mucosa of one patient revealed that NR0B2 downstream targets, SMAD3 was derepressed while GLI1 was downregulated in the colonic mucosa compared to healthy controls. Truncated NR0B2 molecule was predicted to have weakened binding with interacting partners SMAD3, GLI1, BCL2, and RXRα, implying perturbation of TGF-β, Hedgehog, anti-apoptotic and nuclear hormone receptor signaling pathways. Immunostaining also revealed nuclear retention of the most severely truncated NR0B2 molecule compared to the wildtype. Microsatellite and sequencing analysis did not detect loss of wildtype allele in probands' tumors. The patient who acquired somatic KRAS mutation progressed rapidly whist the other two patients manifested with late-onset obesity and diabetes. We propose that haploinsufficiency of NR0B2 is associated with a novel CRC syndrome with metabolic phenotypes., (© 2020 Wiley Periodicals LLC.)

Background: As a consequence of the improvement in survival after solid organ transplantation, to visit transplant recipients with neoplastic and non-neoplastic skin disorders due to immunosuppressive treatment has become common for dermatologists., Methods: Our endpoints were: 1) to investigate the most common skin diseases in a population of transplant recipients; 2) their associations with the type of immunosuppressant or transplant received; and 3) to compare our single center 40-year experience with the literature data. We retrospectively analyzed the clinical details of the adult patients transplanted in the years 1974-2014, visited for consultation at the Unit of Dermatology of our hospital., Results: Pathologic conditions were observed in more than 3/4 of 812 adults during the follow-up (mean 12.1 years): nonmelanoma skin cancers or actinic keratoses were seen in 44.0% (N.=357) of patients, non-neoplastic events in 55.2% (N.=448). Heart transplant had the statistically significant highest rate of NMSC and AK (52.6%, P=0.0352). Patients receiving cyclosporine A developed at least one non-melanoma skin cancer or actinic keratosis in 57.7% of cases (P=0.0001), while tacrolimus showed a lower risk (33%, P=0.0001)., Conclusions: As transplant recipients are susceptible to skin changes, especially after immunosuppressant treatments, a dermatological follow-up should be scheduled for each patient.

Background and Purpose: Burn patients are at a higher risk of infections caused by different organisms. This study aimed to address the prevalence, causative species, and factors related to fungal colonization or infection in patients with acute severe injuries admitted to the intensive care unit (ICU) of a burn hospital in northern Vietnam., Materials and Methods: This prospective study was conducted on 400 patients in a burn ICU between 2017 and 2019. Clinical samples were weekly collected and screened for fungi, and relevant clinical information was obtained from medical records., Results: According to the results, 90% of the patients were colonized with fungi. Out of this group, 12.75% of the cases had invasive fungal infection (IFI). Eleven yeasts and six mold species were isolated from the patients, with the most common species being Candida tropicalis (45.56%) and C. albicans (41.94%). Among the eleven species causing fungal wound infection (FWI), the most common agents were Candida (66.7% of FWI patients) and Aspergillus (38.5%) species. Three Candida species isolated from blood were C. tropicalis (66.7%), C. albicans (20.0%), and C. parapsilosis (14.3%). No factors were found to expose the patients to a higher risk of fungal colonization. However, hyperglycemia, prolonged ICU stay, and heavy Candida species colonization were found to be independently predictive of IFI., Conclusion: Burn patients are at the risk of fungal infection with Candida species (especially C. tropicalis ) and Aspergillus as the most frequently responsible agents. Continuous surveillance of fungi and appropriate management of pathophysiological consequences are essential to prevent fungal infection in burn patients., (Copyright: © 2020, Published by Mazandaran University of Medical Sciences on behalf of Iranian Society of Medical Mycology and Invasive Fungi Research Center.)

Cerebral cysticercosis is the most common parasitic disease of the human nervous system. It is endemic to some tropical countries but has rarely been described in Vietnam. We report three cases of neurocysticercosis in patients from north-west Vietnam presenting with recurrent epileptic seizures. Hypereosinophilia and positive immunoglobulin G (IgG) antibodies to cysticercosis were detected in two patients and three patients, respectively. The brain MRI showed multiple ring-enhancing cerebral lesions with a well-defined border. Scolexes were demonstrated on fluid attenuation inversion recovery (FLAIR) sequence as small images associated with a hyperintense cyst wall. Treatment of cerebral cysticercosis infection with albendazole 15 mg/kg/day x 21 days along with antiepileptic drug therapy usually results in a favorable outcome. These results highlight that cerebral cysticercosis should be suspected in patients from an endemic area who present with headaches and/or epileptic seizures., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Hong Van et al.)

Background: Mucous membrane pemphigoid (MMP) is a heterogeneous group of blistering disorders affecting the mucosae with or without skin involvement, characterized by the presence of autoantibodies to components of the basement membrane zone, including the bullous pemphigoid antigen BP180 and β4 integrin. Current literature has shown that a minority of patients present circulating antibodies to laminin-332 and this population seems to be associated with a relatively high risk of malignancy., Objective: To present our personal case series of patients with MMP-associated malignancy from a dermatology university hospital., Methods: Twenty-two patients affected by MMP were seen in the period between 2001 and 2016; in 4 patients (18%) an associated cancer was detected., Results: These patients were 2 men and 2 women, with a mean age of 69.7 years (range, 48-83). The associated malignancies included a breast cancer, a pancreatic adenocarcinoma, a metastatic laryngeal carcinoma, and a hepatic carcinoma. All patients had negative results for both BP180 and laminin-332 autoantibodies., Conclusion: We confirm that MMP patients have a relatively high possibility of developing a solid cancer, but the autoantibody detection is not mandatory and is probably correlated with the severity of the disease., Competing Interests: Competing interests: The authors have no conflicts of interest to disclose.

This work reports the results and the comparison concerning the chemical and biomolecular analyses and the antifungal activity of three wild Pistacia species (Anacardiaceae) from Sardinia. Volatile oils from leaves and twigs of Pistacia x saportae, Pistacia lentiscus and Pistacia terebinthus were characterised using GC-FID and GC-MS techniques and tested against some fungal strains. Two DNA nuclear regions (ITS and 5S-rRNA-NTS) were amplified through PCR technique and sequenced. The three **Pistacia have similar chemical profile, although there are some important quantitative differences. The analysis of ITS and 5S-rRNA-NTS regions, reveals a species-specific nucleotide variation among the three **taxa. This method could emerge as a powerful tool for the species identification, especially because the discrimination of these three **taxa appears difficult for non-expert botanists. Concerning the antifungal activity, P. lentiscus and P. x saportae show the highest activity against Cryptococcus neoformans, with a MIC value of 0.32 μL/mL.

Introduction: National data on the epidemiology of cancer are commonly reported by broad racial/ethnic categories, such as "Hispanic." However, few studies have disaggregated Hispanic groups and explored mortality differentials in this heterogeneous population. This paper aims to further examine cancer mortality differentials among Hispanic subgroups in the U.S. Materials and Methods: The study examined cancer deaths in the United States from 2004 to 2014 among decedents classified as Mexican, Puerto Rican, Cuban, Dominican, Central/South American and non-Hispanic white on the death certificate among those who were 20 years or older at the time of death. Data were obtained from the National Vital Statistics System. Sex-specific age-adjusted mortality rates were computed for a 10-year period and each individual year, for all cancers combined. Differences by age group, cancer sites, and age distribution were also assessed. Results: A total of 296,486 Hispanic cancer deaths were identified. Mortality rates of the Hispanic subgroups compare favorably with those of non-Hispanic whites. The mortality rates for Mexicans are very similar to those of all Hispanics combined, whereas the rates for Cuban and Puerto Ricans are higher. Dominicans and Central/South Americans had the overall lowest mortality rates. Statistically significant decreases in cancer mortality rates were noted in some sub-groups, but rates increased among Dominican women. Age-adjusted mortality rates by cancer site varied among Hispanics subgroups and gender. Among Cubans, only 5% of cancer deaths occurred before the age of 50 compared to 16% of cancer deaths among Central/South American. Conclusion: While it is common to present data on the burden of cancer among Hispanics as an aggregate group, this study illustrates that the burden of cancer varies by Hispanic subgroups. The disaggregation of Hispanics by ancestry/country of origin allows for a clearer understanding of the health status of this growing population and is needed if health disparities are to be adequately identified, understood and addressed.

The co-occurrence of depression and chronic diseases is often under-recognized, under-treated, and under-studied. Among Latinos, complex structural and cultural barriers exist which complicate the translation of chronic disease self-management programs (CDSMP) for this population. To better understand those barriers and deliver a CDSMP designed to best meet local needs, a community-based, mixed methods study was designed. Formative research was conducted through focus groups with Latinos with chronic illness and minor depression (ICD) and family members to obtain insight into perceived needs and interviews with stakeholders to assess barriers and facilitators to the adoption of CDSMPs. Analytic Hierarchy Process was employed to determine core elements of a CDSMP for ICDs, family members, and the promotores who deliver these programs. Findings guided the transcreation of a CDSMP. This study offers a promising model for enhancing the effects of evidence-based interventions and emphasizes the importance of meeting differing needs within the local population.

Background: Erosive pustular dermatosis of the scalp is a chronic eruption that leads to scarring alopecia., Objective: The clinical, dermoscopic, and histopathological features and the course of the disease in 20 patients were reviewed and compared with the reports in the literature., Methods: Gender, age at diagnosis, age at onset, duration, topography, predisposing factors, concomitant diseases, trichoscopy, histology, treatment, and outcome were taken into consideration., Results: The mean age was 59.4 years. Androgenetic alopecia was present in 12 patients, 6 of whom showed actinic damage. Trauma was reported in 9 patients. Four patients were affected by autoimmune disorders. The vertex was the most common location. In all 20 patients trichoscopy showed an absence of follicular ostia with skin atrophy. Histopathology revealed 3 different features, depending on the disease duration. A reduction of inflammatory signs was observed in 14 patients treated with topical steroids and in all 3 patients treated with topical tacrolimus 0.1%., Limitations: The rarity of this disease is a limitation., Conclusions: The relatively high number of patients allowed us to identify a better diagnostic approach, using trichoscopy, and a more effective therapeutic strategy, with high-potency steroids or tacrolimus, which should be considered as first-line treatment., (Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Familial adenomatous polyposis (FAP) is an autosomal-dominantly inherited form of colorectal cancer (CRC) caused by mutation in the adenomatous polyposis coli (APC) gene. Our ability to exhaustively screen for APC mutations identify microsatellite-stable and APC-mutation negative familial CRC patients, enabling us to search for novel genes. We performed genome-wide scan on two affected siblings of one family and 88 ethnicity- and gender-matched healthy controls to identify deletions shared by the siblings. Combined loss of heterozygosity, copy number and allelic-specific copy number analysis uncovered 5 shared deletions. Long-range polymerase chain reaction (PCR) confirmed chromosome 19q13 deletion, which was subsequently found in one other family. The 32 kb deleted region harbors the CYP2A7 gene and was enriched with enhancer, repressor and insulator sites. The wildtype allele was lost in the polyps of the proband. Further, real-time RT-PCR assays showed that expressions of MIA and MIA-RAB4B located 35 kb upstream of the deletion, were up-regulated in the polyps compared to the matched mucosa of the proband. MIA-RAB4B, the read-through long non-coding RNA (lncRNA), RAB4B, PIM2 and TAOK1 share common binding site of a microRNA, miR-24, in their 3'UTRs. PIM2 and TAOK1, two target oncogenes of miR-24, were co-ordinately up-regulated with MIA-RAB4B in the polyps, suggesting that MIA-RAB4B could function as competitive endogenous RNA to titrate miR-24 away from its other targets. The data suggest that the 19.13 deletion disrupted chromatin boundary, leading to altered expression of several genes and lncRNA, could contribute to colorectal cancer via novel genetic and epigenetic mechanisms.

Informal caregiving can be fundamental to disease management. Yet, the psychosocial, physical, and financial burden experienced by caregivers can be significant. In the US, Latinos experience increasing rates of chronic conditions, the highest uninsured rates in the country, and a growing dependence on informal caregivers. This article explores the impact of caregiving on caregivers of individuals with comorbid chronic disease and depression. Findings highlight the impact of caregiving on financial insecurity, balancing competing demands, increased emotional distress, and community supports. Findings support the inclusion of caregivers in disease management programs to enhance psychosocial outcomes for both caregivers and their patients.

Germline mutation in the adenomatous polyposis coli (APC) gene causes the majority (80%) of familial adenomatous polyposis (FAP), an autosomal dominantly inherited form of colorectal cancer (CRC). Mutation in 5'end of exon 9 of APC usually results in an attenuated form of FAP (aFAP), characterized by later age of onset and fewer polyps. The presence of exon 9a, an in-frame isoform with exon 8 spliced to 3'end of exon 9, modulates any deleterious effect of the mutation. A third lowly expressed isoform that completely skips exon 9 is present in both healthy individuals and FAP patients. We report here an interesting case of a proband with an APC mutation in 5'end of exon 9 that presented with six synchronous advanced CRCs at age 37. The novel insertion-deletion (indel) at codon 409, c.1226-1229delTTTTinsAAA, caused upregulation of the 'skip exon 9' isoform, r934-1312del, resulting in a premature stop codon at exon 10 and a truncated protein that removed all of the β-catenin (CTNNB1) binding motifs, thus activating the downstream T-cell transcription factor (Tcf) pathway. Exon 9a isoform was concomitantly downregulated. This finding emphasizes the necessity of examining the various isoforms of exon 9 to avoid clinical mismanagement and counseling based on just the mutation site by genomic DNA sequencing alone.

This HPLC method, with both variable UV and fluorescence detection, allows for the simultaneous determination of vitamin A palmitate, vitamin A acetate, and total vitamin E in infant, pediatric, and adult nutritional formulas. The concentration of each vitamin form is calculated by comparison with standards of known concentration. Following hydrolysis, the vitamins are extracted into iso-octane and analyzed by normal phase (NP) HPLC. The method was evaluated for linearity, precision, and accuracy using a selection of the Stakeholder Panel on Infant Formula and Adult Nutritionals (SPIFAN) matrixes, including milk-based, soy-based, and hydrolyzed protein, as well as high- and low-fat products. A single-laboratory validation has been completed for all analytes using a selection of SPIFAN matrixes. Performance parameters included a working range of 2-450 microg/100 g ready-to-feed for vitamin A and 0.03-8.0 mgl100 g reconstituted final product for vitamin E. LOD was <1.0 microg and <0.1 mgl100 g reconstituted final product for vitamins A and E, respectively; RSD was 1.08-8.70% over a range of concentration; and average recoveries of 97.4-101.3%. Repeatability of <4% for vitamin A and <8% for vitamin E was calculated from five laboratories using this method. Results indicate that this method is suitable for the analysis of vitamins A and E in all forms of infant, adult, and pediatric formulas (powders, ready-to-feed liquids, and liquid concentrates). The Expert Review Panel (ERP) of Infant Formula reviewed this method separately for vitamins A and E, including all available method validation data at the AOAC INTERNATIONAL Annual Meeting on September 29, 2012. Following evaluation of the data for both methods, the ERP agreed that both methods met the standard method performance requirements articulated by SPIFAN. The ERP granted First Action status to both methods, and recommended that a single method be published for the simultaneous determination of vitamin A palmitate, vitamin A acetate, and total vitamin E (DL-a-tocopherol and DL-alpha-tocopherol acetate) in infant formula and adult nutritionals by NP HPLC.

Objectives: Hereditary mixed polyposis syndrome (HMPS) is characterized by polyps of mixed adenomatous/hyperplastic/atypical juvenile histology that are autosomal dominantly inherited and that eventually lead to colorectal cancer (CRC). Although CRC with adenomatous polyps is initiated by inactivating adenomatous polyposis coli (APC), the initiating event of CRC with mixed polyps remains unclear. We aimed to identify the underlying germline defect in HMPS., Methods: We screened for bone morphogenesis protein receptor 1A (BMPR1A) mutation by exonic sequencing, reverse-transcriptase polymerase chain reaction (PCR) followed by cDNA sequencing, and multiplex ligation-dependent probe amplification (MLPA) analysis in eight Singapore Chinese HMPS families., Results: Germline BMPR1A defects were found in four (50%) families. In two families, it is shown to co-segregate with the disease phenotype in all affected members over three generations, indicating that it is the disease-causing mutation. CRC incidence is 75%. The most defining characteristic is the presence of mixed hyperplastic-adenomatous polyps. Juvenile polyps are rarely reported, and if present, are usually of mixed components. Detailed histology of the polyps from one patient over 11 years distinguishes HMPS from juvenile polyposis syndrome (JPS). We report further the first cases of Wilms' tumor and papillary thyroid carcinoma associated with BMPR1A germline defect., Conclusions: Germline BMPR1A defect is the disease-causing mutation in 50% of the HMPS families. If patients present with mixed morphology polyps in the large bowel that are autosomal dominantly inherited and corresponding absence of upper gastrointestinal abnormalities, the gene to begin mutation screening should be BMPR1A rather than APC.

Aim of the present phase II non-randomized study was to verify whether palonosetron might be able to prevent acute and especially delayed CINV for either HEC or MEC, starting from the second chemotherapy cycle, in patients who had failed to respond to a different antiemetic 5-HT(3) antagonist during the first cycle. Stratification factor was age <65 years vs. > or =65 years of patients included. Forty-seven cancer patients (23 elderly and 24 non-elderly) scheduled to receive HEC or MEC regimens who had experienced CINV grade 3-4 during the first chemotherapy course and for whom the same course of chemotherapy regimen was further scheduled were enrolled. Complete response (CR) and complete control (CC) rates for the acute, delayed and overall phases of CINV were not significantly different between elderly and non-elderly patients. Palonosetron was safe: only grade 1-2 toxicities were observed with a peak of 12.9% for asthenia with no significant difference between elderly and non-elderly patients. In conclusion, single dose palonosetron (250 microg) should be considered a safe and effective second generation 5-HT(3) antagonist in the prevention of nausea and vomiting induced by HEC or MEC, irrespective of patients' age.

Purpose: This study examined the mutational profile of the adenomatous polyposis coli gene in relation to the development of desmoid tumors in familial adenomatous polyposis patients from a predominantly Chinese population., Methods: This is a retrospective review of all patients with familial adenomatous polyposis coli from the Singapore Polyposis Registry. Identification of specific adenomatous polyposis coli gene mutation was performed and clinical course of associated desmoid disease obtained from case records and a computerized database., Results: Two hundred five patients from 75 families afflicted with familial adenomatous polyposis coli were reviewed, with gene mutations identified in 107 patients. Of these, 23 (11.2 percent) developed desmoids. The male-to-female ratio was 1:1.3 and the ethnic distribution was Chinese (n=17) and Malay (n=6). Of the 92 patients with mutations 5' to codon 1444, 11 patients (12 percent) developed desmoids compared with 6 of 15 (40 percent) patients with adenomatous polyposis coli gene mutations 3' to codon 1444 (P<0.01). The clinical course of desmoid tumors can be divided into stable (n=11), variable (n=3), progressive (n=6), and aggressive growth (n=3). Only 3 (13 percent) patients with aggressive tumor growth required chemotherapy. There was no correlation between the site of mutation and the clinical progression of the desmoids. Seventy-four percent of these desmoids (17/23) developed at a mean interval of 2.98 years after restorative proctocolectomy, while only 30 percent (7/23) were diagnosed preoperatively or discovered during the initial surgery. The most common complications related to the mesenteric desmoids were intestinal obstruction (21.7 percent), ureteric obstruction (17.4 percent), and encasement of superior mesenteric vessels (13 percent)., Conclusion: The clinical course of desmoids in an individual familial adenomatous polyposis patient remains unpredictable and no reliable genetic marker is available for prognostication in desmoid disease.

Objectives: Germline mutation in adenomatous polyposis coli (APC) is detected in up to 80% of familial adenomatous polyposis (FAP) patients worldwide. In this study, we evaluated clinical features and APC mutations of Singapore FAP patients and contrasted genotype-phenotype correlation with Caucasians from other regions of the world and between FAP patients with and without detectable APC mutations., Methods: We screened 242 members from 57 unrelated FAP families using a combination of cDNA protein truncation test, multiplex ligation-dependent probe amplification, and differential expression techniques., Results: APC germline mutations were detected in 50 families. In contrast to Caucasians, fundic gland polyposis in Singapore patients was associated with APC mutations throughout the coding region and osteomas were also not confined to codon 767-1573. There was also no FAP-associated hepatoblastoma or medullablastoma. APC mutation-negative patients from four families with mixed (adenomatous/hyperplastic/atypical juvenile) polyps were subsequently reclassified as hereditary mixed polyposis syndrome (HMPS) patients. APC mutation-negative patients with classical adenomatous polyposis were negative for MYH, beta-catenin, and Axin 1 mutations. These patients had a significantly older age at diagnosis (P < 0.001) and more colorectal cancers (P= 0.017) than patients with APC mutations., Conclusions: We achieved a 94% (50/53) APC mutation detection rate via a combination of techniques, suggesting that the current detection rate is probably not exhaustive. Singapore patients have some features similar to and other features distinct from Caucasians. Furthermore, APC mutation-negative patients have accelerated cancer progression that merits closer surveillance.

We investigated whether a single plasma midazolam concentration could serve as an accurate predictor of total midazolam clearance, an established in-vivo probe measure of cytochrome P450 3A (CYP3A) activity. In a retrospective analysis of data from 224 healthy volunteers, non-compartmental pharmacokinetic parameters were estimated from plasma concentration-time curves following intravenous (IV) and/or oral administration. Based on statistical moment theory, the concentration at the mean residence time (MRT) should be the best predictor of the total area under the curve (AUC). Following IV or oral midazolam administration, the average MRT was found to be approximately 3.5 h, suggesting that the optimal single sampling time to predict AUC was between 3 and 4 h. Since a 4-h data point was common to all studies incorporated into this analysis, we selected this time point for further investigation. The concentrations of midazolam measured 4 h after an IV or oral dose explained 80 and 91% of the constitutive interindividual variability in midazolam AUC, respectively. The 4-h midazolam measurement was also an excellent predictor of drug-drug interactions involving CYP3A induction and inhibition. Compared with baseline values, the direction and magnitude of change in midazolam AUC and the 4-h concentration were completely concordant for all study subjects. We conclude that a single 4-h midazolam concentration following IV or oral administration represents an accurate marker of CYP3A phenotype under constitutive and modified states. Moreover, the single-point approach offers an efficient means to phenotype and identify individuals with important genetic polymorphisms that affect CYP3A activity.