Activity Limitation Counseling in Dermatologic Surgery: A Survey and Retrospective Chart Review.

INTRODUCTION: Perioperative counseling regarding activity limitations is critical for patients undergoing dermatologic surgery. Current postoperative instructions regarding activity limitations may be inadequate, but this cannot be determined without knowing patient expectations. The study objective was to elucidate patient expectations for counseling on postoperative activity limitations and to determine if increased counseling would impact patient planning pre or postoperatively. MATERIALS AND METHODS: Patients who had excisions on the neck, torso, or extremities at one institution in one calendar year by the same surgeon participated in a phone survey. Questions addressed preexisting activity level, activity changes after surgery, amount of counseling received, and perioperative counseling expectations. Multivariable logistic regression was used to determine factors associated with patient perceptions about counseling, activity limitations, and surgical outcomes. RESULTS: Patients counseled on postoperative activity limitations reported they were unlikely to have made further arrangements to their surgical/personavl schedule had they been given additional counseling. The inverse was also true. When patients received the amount of counseling they expected, they were less likely to want to reschedule surgery or adjust personal plans. Younger patients and those with surgery on the lower extremities were more likely to limit their activity for longer periods of time. CONCLUSIONS: As instructions on activity limitations become more transparent, patients can make informed decisions regarding their surgical and personal schedules. This study can guide dermatologic surgeons in adjusting postoperative instructions to improve patient understanding of activity limitations, compliance, and the overall quality of their surgical experience.

The 730 nm picosecond titanium sapphire laser for treatment of café-au-lait macules in all skin types.

OBJECTIVES: Café-au-lait macules (CALM) are benign birthmarks presenting as uniformly pigmented, well demarcated, brown patches that can be distressing to patients, especially when located in cosmetically sensitive areas. As with all pigmentary lesions in skin of color patients, CALMs have been particularly challenging to treat. Here we present the first case series characterizing treatment parameters and clinical outcomes utilizing the 730-nm picosecond titanium sapphire laser for the treatment of CALMs. This device provides an additional safe and effective treatment option for these challenging cases. METHODS: We performed a retrospective review of patients treated at a single institution between April 2021 and December 2023. Clinical photographs were graded by 3 outside board-certified dermatologists using a 5-point visual analog scale. RESULTS: Fourteen patients (age range: 10 months-66 years, mean age: 27.4 years, Fitzpatrick skin types II-VI) were treated for CALM on the face (11) or body (3). On average, patients received 4.3 treatments, with treatment intervals ranging from 4 to 40 weeks. Treatment remains ongoing with the 730-nm picosecond laser for eight patients. Overall, patients were rated to have a mean improvement of 26%-50%. Two patients (FST III and VI) achieved 100% clearance after 4-5 treatment sessions. Our study included four patients whose CALM were of the smooth bordered "coast of California" subtype, three of whom had a mean improvement rating of only 1%-25%. The fourth patient had near complete resolution. Follow up for these patients has ranged from 6 weeks to 1.5 years. Of the patients treated, one patient experienced transient post-inflammatory hyperpigmentation and another transient post-inflammatory hypopigmentation, while a third patient experienced mild persistent guttate hypopigmentation. Three patients experienced partial recurrence indicating that maintenance treatments may be needed in some patients. CONCLUSION: The 730-nm picosecond titanium sapphire laser is a safe and efficacious treatment option, in the right morphologic setting, to improve the cosmetic appearance of CALMs in a wide range of ages and skin types. To our knowledge, this is the first reported treatment of CALMs with picosecond lasers in FST V and VI patients. Our study also supports prior studies which have found that CALM with smooth-bordered "coast of California" morphology have a poor response to laser therapy as compared to those with jagged or ill-defined bordered "coast of Maine" morphology.

Paired guide RNA CRISPR-Cas9 screening for protein-coding genes and lncRNAs involved in transdifferentiation of human B-cells to macrophages.

CRISPR-Cas9 screening libraries have arisen as a powerful tool to identify protein-coding (pc) and non-coding genes playing a role along different processes. In particular, the usage of a nuclease active Cas9 coupled to a single gRNA has proven to efficiently impair the expression of pc-genes by generating deleterious frameshifts. Here, we first demonstrate that targeting the same gene simultaneously with two guide RNAs (paired guide RNAs, pgRNAs) synergistically enhances the capacity of the CRISPR-Cas9 system to knock out pc-genes. We next design a library to target, in parallel, pc-genes and lncRNAs known to change expression during the transdifferentiation from pre-B cells to macrophages. We show that this system is able to identify known players in this process, and also predicts 26 potential novel ones, of which we select four (two pc-genes and two lncRNAs) for deeper characterization. Our results suggest that in the case of the candidate lncRNAs, their impact in transdifferentiation may be actually mediated by enhancer regions at the targeted loci, rather than by the lncRNA transcripts themselves. The CRISPR-Cas9 coupled to a pgRNAs system is, therefore, a suitable tool to simultaneously target pc-genes and lncRNAs for genomic perturbation assays.

Intracranial hemangioma-associated cranial nerve VII palsy treated with propranolol in an infant with possible PHACE syndrome.

A 2-week-old infant with a large vascular birthmark involving her right face presented with right-sided facial paralysis. MRI of the brain revealed multiple intracranial hemangiomas, and the hemangioma within the right temporal bone impinged on the facial nerve, which resulted in paralysis. Cranial nerve palsies are a rare neurological manifestation of PHACE syndrome. We report successful treatment of the facial nerve palsy with oral propranolol.

Systematic review of universal family prevention programs: Analysis in terms of efficacy, retention and adherence. / Revisión sistemática de programas de prevención familiar universal: Análisis en términos de eficacia, retención y adherencia.

Adherence is an important aspect of the effectiveness of family interventions for universal drug prevention. Some approaches suggest adherence assessments should be improved because they are partial and do not take into account all dimensions. The objective of the study is to analyze adherence and retention measures used in family intervention programs for the prevention of substance use in young people aged 10-14 years. To this end, the literature was reviewed on universal programs which have obtained good preventive results. The information sources consulted are: PubMed, PsycINFO (EBSCO), PsycArticles (EBSCO), Social Work abstracts (EBSCO), CINAHL (EBSCO) SocIndex (EBSCO), Scopus, Academic Search Premier (EBSCO), SCIC-ISOC, Cochrane Database of Systematic Reviews, ERIC, ScienceDirect, Web of Science, Project Cork, Researchgate, and consultation with experts. The search results show 21 studies belonging to 6 family programs: Strengthening Families Program 10-14, Parents Who Care, Family Check-Up, Linking Lives Health, Prevention of Alcohol use in Students, and Örebro Prevention Program. The studies analyzed provide little information on the different elements involved in adherence. Retention and differential attribution are the data that appear most frequently, while other aspects such as active participation do not appear in the studies. The results are discussed and recommendations are made to improve the evaluation of adherence and retention in family prevention programs.

La adherencia es un aspecto importante para la eficacia de las intervenciones familiares de prevención universal de drogas. Algunas aproximaciones sugieren mejorar las evaluaciones sobre adherencia, ya que resultan parciales y no tienen en cuenta todas sus dimensiones. El objetivo del estudio es analizar las medidas de adherencia y retención utilizadas en los programas de intervención familiar para la prevención del consumo en jóvenes de 10-14 años. Para ello se revisa la literatura sobre programas universales que han obtenido buenos resultados preventivos. Las fuentes de información consultadas son: PubMed, PsycINFO (EBSCO), PsycArticles (EBSCO), Social Work abstracts (EBSCO), CINAHL (EBSCO) SocIndex (EBSCO), Scopus, Academic Search Premier (EBSCO), SCIC-ISOC, Cochrane Database of Systematic Reviews, ERIC, ScienceDirect, Web of Science, Project Cork, Researchgate y consulta expertos. Los resultados de la búsqueda muestran 21 estudios que pertenecen a 6 programas familiares: Strengthening Families Programme 10-14, Parents Who Care, Family Check-Up, Linking Lives Health, Prevention of Alcohol use in Students y Örebro Prevention Program. Los estudios analizados aportan poca información sobre los diferentes elementos involucrados en la adherencia. La retención y la atricción diferencial son los datos que aparecen con mayor frecuencia, mientras que otros aspectos como la participación activa no aparecen en los estudios. Se discuten los resultados y se realizan recomendaciones para mejorar la evaluación de la adherencia y retención en los programas de prevención familiar.

Incisional biopsy critical in obtaining definitive diagnosis in a clinically challenging case.

Tissue-sparing biopsy techniques are frequently used in clinical practice but can result in misdiagnosis of large, clinically challenging lesions. We present a case of a 70-year-old man with hidradenocarcinoma of the left chin, a diagnosis that was delayed owing to repeated superficial biopsies that were negative for disease. Diagnosis was ultimately obtained via an incisional biopsy. We discuss the clinical features of hidradenocarcinoma and why this diagnosis can be easily missed with superficial biopsies. It is important that dermatologists consider incisional biopsies in the workup of clinically challenging lesions for which malignancy is considered.

A novel inhaled Syk inhibitor blocks mast cell degranulation and early asthmatic response.

Spleen tyrosine kinase (Syk) is essential for signal transduction of immunoreceptors. Inhibition of Syk abrogates mast cell degranulation and B cell responses. We hypothesized that Syk inhibition in the lung by inhaled route could block airway mast cells degranulation and the early asthmatic response without the need of systemic exposure. We discovered LAS189386, a novel Syk inhibitor with suitable properties for inhaled administration. The aim of this study was to characterize the in vitro and in vivo profile of LAS189386. The compound was profiled in Syk enzymatic assay, against a panel of selected kinases and in Syk-dependent cellular assays in mast cells and B cells. Pharmacokinetics and in vivo efficacy was assessed by intratracheal route. Airway resistance and mast cell degranulation after OVA challenge was evaluated in an ovalbumin-sensitized Brown Norway rat model. LAS189386 potently inhibits Syk enzymatic activity (IC50 7.2 nM), Syk phosphorylation (IC50 41 nM), LAD2 cells degranulation (IC50 56 nM), and B cell activation (IC50 22 nM). LAS189386 inhibits early asthmatic response and airway mast cell degranulation without affecting systemic mast cells. The present results support the hypothesis that topical inhibition of Syk in the lung, without systemic exposure, is sufficient to inhibit EAR in rats. Syk inhibition by inhaled route constitutes a promising therapeutic option for asthma.

Two Cases of Pigmented Basal Cell Carcinoma in African American Patients.

Basal cell carcinoma (BCC) is the most common cutaneous malignancy, comprising approximately 80% of non-melanoma skin cancers. There are numerous subtypes, including pigmented basal cell carcinoma (pBCC), a rare clinical and histological variant. Skin cancers in African American patients, although rare, still do occur. BCC is an uncommon neoplasm in this population, but when it does occur, pigmentation is present in more than 50% of tumors compared with only 5% to 6% of BCCs in Caucasians. This report presents two cases of histologically verified pBCC in African American patients from dermatology clinics at the Veterans Affairs Hospital located in the Texas Medical Center. With the population of the United States growing more diverse, these cases emphasize the importance of recognizing the nuanced morphology of BCC in the skin of color compared to lighter-skinned counterparts. This is especially necessary, as early detection and prompt management are key to combating the disproportionately high morbidity and mortality related to skin cancers affecting patients of color.

Nucleosides are overlooked fuels in central carbon metabolism.

From our daily nutrition and synthesis within cells, nucleosides enter the bloodstream and circulate throughout the body and tissues. Nucleosides and nucleotides are classically viewed as precursors of nucleic acids, but recently they have emerged as a novel energy source for central carbon metabolism. Through catabolism by nucleoside phosphorylases, the ribose sugar group is released and can provide substrates for lower steps in glycolysis. In environments with limited glucose, such as at sites of infection or in the tumor microenvironment (TME), cells can use, and may even require, this alternative energy source. Here, we discuss the implications of these new findings in health and disease and speculate on the potential new roles of nucleosides and nucleic acids in energy metabolism.

Two-Step Tag-Free Isolation of Mitochondria for Improved Protein Discovery and Quantification.

Most physiological and disease processes, from central metabolism to immune response to neurodegeneration, involve mitochondria. The mitochondrial proteome is composed of more than 1,000 proteins, and the abundance of each can vary dynamically in response to external stimuli or during disease progression. Here, we describe a protocol for isolating high-quality mitochondria from primary cells and tissues. The two-step procedure comprises (1) mechanical homogenization and differential centrifugation to isolate crude mitochondria, and (2) tag-free immune capture of mitochondria to isolate pure organelles and eliminate contaminants. Mitochondrial proteins from each purification stage are analyzed by quantitative mass spectrometry, and enrichment yields are calculated, allowing the discovery of novel mitochondrial proteins by subtractive proteomics. Our protocol provides a sensitive and comprehensive approach to studying mitochondrial content in cell lines, primary cells, and tissues.

Dead-Seq: Discovering Synthetic Lethal Interactions from Dead Cells Genomics.

Pooled genetic screens have revolutionized the field of functional genomics, yet perturbations that decrease fitness, such as those leading to synthetic lethality, have remained difficult to quantify at the genomic level. We and colleagues previously developed "death screening," a protocol based on the purification of dead cells in genetic screens, and used it to identify a set of genes necessary for mitochondrial gene expression, translation, and oxidative phosphorylation (OXPHOS), thus offering new possibilities for the diagnosis of mitochondrial disorders. Here, we describe Dead-Seq, a refined protocol for death screening that is compatible with most pooled screening protocols, including genome-wide CRISPR/Cas9 screening. Dead-Seq converts negative-selection screens into positive-selection screens and generates high-quality data directly from dead cells, at limited sequencing costs.

Results of a Community-Based Screening Program for Chlamydia trachomatis Genital Infection in Young People Aged 18-25 Years.

Introduction and aim Chlamydia trachomatis (CT) cases have increased in the last decade. The aim of the study was to assess the prevalence of CT genital infection in asymptomatic, sexually active young people and determine whether a community screening program would be effective in reducing the number of cases. Methods A descriptive cross-sectional studyof consecutive inclusion of asymptomatic people aged 18-25 years between September 2021 and May 2022. Community interventions in high schools, universities, and cultural events were planned to realize the screening. Sociodemographic variables of gender, age, country of origin, and educational level, as well as sexual habits, were recorded for each patient. CT was detected via urine samples. An estimate of the prevalence of CT genital infection and its 95% confidence interval (CI) was made based on the exact binomial distribution, assuming that the sample is representative of the study population. Results A total of 628 subjects participated in the study, of whom 33 had a CT infection, giving a prevalence of 5.2% (95% CI: 3.6%, 7.3%). 93.9% of subjects with CT infection were female (p≤0.019) and 85% of the participants were Spanish nationals. Among vocational training students, the prevalence was 8.1%. Having had four or more sexual partners in the last month and in the previous year was significantly associated with CT infection (p<0.001). Conclusion Screening for CT genital infection in young sexually active women should be implemented in our country, as recommended by the various guidelines.

Salvage of ribose from uridine or RNA supports glycolysis in nutrient-limited conditions.

Glucose is vital for life, serving as both a source of energy and carbon building block for growth. When glucose is limiting, alternative nutrients must be harnessed. To identify mechanisms by which cells can tolerate complete loss of glucose, we performed nutrient-sensitized genome-wide genetic screens and a PRISM growth assay across 482 cancer cell lines. We report that catabolism of uridine from the medium enables the growth of cells in the complete absence of glucose. While previous studies have shown that uridine can be salvaged to support pyrimidine synthesis in the setting of mitochondrial oxidative phosphorylation deficiency1, our work demonstrates that the ribose moiety of uridine or RNA can be salvaged to fulfil energy requirements via a pathway based on: (1) the phosphorylytic cleavage of uridine by uridine phosphorylase UPP1/UPP2 into uracil and ribose-1-phosphate (R1P), (2) the conversion of uridine-derived R1P into fructose-6-P and glyceraldehyde-3-P by the non-oxidative branch of the pentose phosphate pathway and (3) their glycolytic utilization to fuel ATP production, biosynthesis and gluconeogenesis. Capacity for glycolysis from uridine-derived ribose appears widespread, and we confirm its activity in cancer lineages, primary macrophages and mice in vivo. An interesting property of this pathway is that R1P enters downstream of the initial, highly regulated steps of glucose transport and upper glycolysis. We anticipate that 'uridine bypass' of upper glycolysis could be important in the context of disease and even exploited for therapeutic purposes.

Good practice regarding smoking cessation management in Spain: Challenges and opportunities for primary care physicians and nurses.

INTRODUCTION: We analyze the activities carried out by primary care (PC) physicians and nurses with respect to smoking cessation and evaluate their self-reported training, knowledge, and behavior. METHODS: A cross-sectional study was conducted including 1514 PC physicians and nurses from June 2016 to March 2017, in Spain. The main variable was Good Practice (GP) in attention to smokers. To identify associated factors, a multilevel logistic regression model was used adjusted for sex, age, type of center, contract, years of employment, tobacco consumption, and self-reported training/knowledge. RESULTS: Of the 792 physicians and 722 nurses, 48.6% referred to GP in smoking cessation management. The finding related to: being a non-smoker (OR=1.8; 95% CI: 1.2-2.5) or ex-smoker (OR=1.4; 95% CI: 1.02-2.1), having a good level of knowledge (OR=1.8; 95% CI: 1.3-2.4) and training (OR=2.4; 95% CI: 1.8-3.2), and, to a lesser extent, being female (OR=1.3; 95% CI: 1.03-1.7), and work experience >10 years (OR=1.4; 95% CI: 1.03-1.9). The main GP barriers were: lack of time (45.5%), organizational problems (48.4%), and 35.4% lack of training. CONCLUSIONS: The GP of PC physicians and nurses regarding smoking cessation management is related to being non-smokers or ex-smokers, and having sufficient training and knowledge. Lack of time and organizational problems were considered to be the main barriers. The promotion of training activities in the Spanish National Health Service with the support of scientific societies is required.

Attitudes towards anti-smoking legislation and prevalence of tobacco consumption in Spanish primary healthcare personnel.

INTRODUCTION: Our aim was to ascertain how the anti-smoking legislation of 2005/2010 has affected the behavior of primary healthcare center (PHC) personnel (medical and nonmedical) with respect to their attitudes towards tobacco, its consumption and the legislative changes. METHODS: We conducted a multi-center descriptive study of a randomized conglomerate sample of PHC personnel from each Autonomous Community in Spain. The questionnaire covered tobacco consumption, and knowledge/attitudes towards smoking and legislation. The statistical analysis used SPSS software. RESULTS: The sample consisted of 2040 PHC employees (1578 women, 77.4%). Never smokers, ex-smokers, and smokers represented 46.7%, 37.8%, and 15.5% of the sample, respectively. Tobacco prevalence amongst physicians and nurses was 12.3%. Following the introduction of the antismoking legislation, a decrease in consumption was observed. Most of the participants considered that tobacco consumption affected health, was an addictive illness, and passive smoking had an impact on the health of non-smokers. Whilst 91.6% agreed with the current legislation, only 25% felt that it encouraged cessation. CONCLUSIONS: Spanish primary healthcare professionals have a relatively low prevalence of smoking compared to the general population. It is necessary to implement more legislative measures to improve and maintain this outcome.

[Hemoglobinopathies and glucose-6-phosphate dehydrogenase deficiency in the sub-Saharan immigrant population of the Center and South Maresme region, Catalonia, Spain]. / Estudio de hemoglobinopatías y del déficit de glucosa-6-fosfato deshidrogenasa en la población inmigrante subsahariana del centro y sur del Maresme (Cataluña).

BACKGROUND AND OBJECTIVE: Prevalence of hemoglobinophaty S and glucose-6-phosphate dehydrogenase (G6PD) deficiency are very increased in certain zones of Western Africa due to the positive pressure exerted by malaria on these congenital defects. In Maresme, a region of East Catalonia, there is a numerous community of African people, coming from areas of Western Africa where sickle cell trait and G6PD deficiency are frequent. The aim of our study was to know the prevalence of both disturbances in this population. POPULATION AND METHOD: We studied 204 individuals of black ethnical background who were migrant Africans. They attended the Immigrant Attention Unit or Outside Surgery Department of Consorcio Sanitario de Mataró for any medical or surgical problems but not for anemia. The G6PD deficiency was determined by a quantitative assay and 2 screening techniques. The identification of abnormal hemoglobins was done by electrophoresis. RESULTS: We studied 141 males (69%) and 63 females (31%). Mean age was 30.8 years (range: 1-70). The studied population came from Gambia, Senegal, Equatorial Guinea, Guinea Bissau, Mali, Somalia, Guinea Conakry, Nigeria, Ghana, Ivory Coast, Sierra Leone, Liberia and Mauritania, and were members of the Sarankhole, Mande, Fulani, Peul, Djola, Bambara, Pare and Ibo ethnic groups (according to the frequency order). We found abnormal hemoglobins in 44 subjects (21.5%): 36 hemoglobin S carriers, 7 hemoglobin C carriers and one hemoglobin C homozygous. Moreover, we identified G6PD deficiency in 31 subjects. According to these results, the prevalence of hemoglobinophaty S in these people is 17.6%; the prevalence of hemoglobinophaty C is 3.9%, and the prevalence of G6PD deficiency is 15.2%. The association of abnormal hemoglobins and G6PD deficiency was found only in a 3% of the cases (2.5% hemoglobinophaty S and 0.5% hemoglobinophaty C). CONCLUSIONS: This results demonstrate a high prevalence of hemoglobinopathies and G6PD deficiency in this population. The morbidity and mortality of sickle cell disease and the complications due to G6PD deficiency, besides the easy detection using electrophoresis and G6PD determination, make it necessary to standardize these tests in areas with high density of black people.

A nonacid degradable linker for solid-phase synthesis.

Synthesis and applications of two new nonacid degradable linkers as an alternative to the Wang linker for solid-phase synthesis are described. Resin from linker 2 looks superior to linker 1 in terms of yields for both anchoring of the first building block and cleavage and in terms of higher purity of the final product. Use of linker 2 avoids side reactions associated with the use of Wang resin due to an undesired cleavage during final acid treatment.

Meta-analysis of family-based selective prevention programs for drug consumption in adolescence.

BACKGROUND: Substance consumption (SC) begins in adolescence and has been linked to protection factors such as family relationships (FR) and positive parenting (PP). There are few studies concerning the effectiveness of prevention programs based on the family, even though assessing interventions is one of the objectives of preventive science. The aim of this study was to analyze the evidence on family-based selective prevention programs in relation to drug consumption in adolescents. METHODOLOGY: A meta-analysis of 9 studies with 102 measures grouped in three dimensions, FR, PP and SC, ranging between 2001 and 2015, was conducted. RESULTS: Effect sizes (ES) were found to be 0.82 for FR, 0.71 for PP, 0.77 for the combination of both and 0.21 for SC. The Q and I2 indexes expressed high heterogeneity. CONCLUSIONS: Despite obtaining high ES consistent with previous studies, the great heterogeneity found did not allow us to draw clear conclusions regarding the primary studies. It is recommended that methodological improvements in assessment and reporting processes be carried out for future comparisons.