Uterine leiomyomata and keloids fibrosis origins: a mini-review of fibroproliferative diseases.

Diseases such as uterine leiomyomata (fibroids and benign tumors of the uterus) and keloids (raised scars) may share common etiology. Fibroids and keloids can co-occur in individuals, and both are highly heritable, suggesting they may share common genetic risk factors. Fibroproliferative diseases are common and characterized by scarring and overgrowth of connective tissue, impacting multiple organ systems. These conditions both have racial disparities in prevalence, with the highest prevalence observed among individuals of African ancestry. Several fibroproliferative diseases are more severe and common in populations of sub-Saharan Africa. This mini-review aims to provide a broad overview of the current knowledge of the evolutionary origins and causes of fibroproliferative diseases. We also discuss current hypotheses proposing that the increased prevalence of these diseases in African-derived populations is due to the selection for profibrotic alleles that are protective against helminth infections and provide examples from knowledge of uterine fibroid and keloid research.

Effect of environmental water activity on microbial inactivation by intense pulsed light (IPL).

In this study, the effect of environmental aw on microbial inactivation by intense pulsed light (IPL) was investigated. Three different microorganisms (Gram-positive bacteria, Gram-negative bacteria, and yeast) were used as test organisms. The effect of environmental aw was assessed by irradiating each microbial suspension in sodium chloride solutions with different environmental aw levels (0.99-0.80). As the aw decreased, the aggregation of intracellular material of cell interior was changed and the cell number was increased. However, there was no significant difference in microbial reduction according to the aw after the 0.23-3.05 J/cm2 of IPL treatment. It was confirmed that yeast had the highest resistance to IPL because of the differences in cell structure and cell wall components between yeast and bacteria. Additional research is needed to clearly understand the inactivation mechanism according to the type of microorganism by controlling aw using various solutes.

EVALUATING THE RELATIONSHIPS BETWEEN GENETIC ANCESTRY AND THE CLINICAL PHENOME.

There is a desire in research to move away from the concept of race as a clinical factor because it is a societal construct used as an imprecise proxy for geographic ancestry. In this study, we leverage the biobank from Vanderbilt University Medical Center, BioVU, to investigate relationships between genetic ancestry proportion and the clinical phenome. For all samples in BioVU, we calculated six ancestry proportions based on 1000 Genomes references: eastern African (EAFR), western African (WAFR), northern European (NEUR), southern European (SEUR), eastern Asian (EAS), and southern Asian (SAS). From PheWAS, we found phecode categories significantly enriched neoplasms for EAFR, WAFR, and SEUR, and pregnancy complication in SEUR, NEUR, SAS, and EAS (p < 0.003). We then selected phenotypes hypertension (HTN) and atrial fibrillation (AFib) to further investigate the relationships between these phenotypes and EAFR, WAFR, SEUR, and NEUR using logistic regression modeling and non-linear restricted cubic spline modeling (RCS). For EAS and SAS, we chose renal failure (RF) for further modeling. The relationships between HTN and AFib and the ancestries EAFR, WAFR, and SEUR were best fit by the linear model (beta p < 1x10-4 for all) while the relationships with NEUR were best fit with RCS (HTN ANOVA p = 0.001, AFib ANOVA p < 1x10-4). For RF, the relationship with SAS was best fit with a linear model (beta p < 1x10-4) while RCS model was a better fit for EAS (ANOVA p < 1x10-4). In this study, we identify relationships between genetic ancestry and phenotypes that are best fit with non-linear modeling techniques. The assumption of linearity for regression modeling is integral for proper fitting of a model and there is no knowing a priori to modeling if the relationship is truly linear.

Hereditary Leiomyomatosis and Renal Cell Cancer: A Case Report of Pilar Leiomyomatosis with History of Kidney Cancer and Review of the Literature.

Pilar leiomyoma or piloleiomyoma is a benign neoplasm of the smooth muscle arising from the arrector pili muscle. It manifests as brown to red firm papulonodules with sites of predilection being the face, trunk, and extensor surfaces of the extremities. Histologically, the lesions exhibit ill-defined dermal tumors with interlacing fascicles of spindle cells. Some genodermatoses are characterized by the development of visceral tumors and cutaneous leiomyomatosis such as Reed's syndrome, and hereditary leiomyomatosis and renal cell cancer (HLRCC). A 55-year-old male presented with reddish-brown papules and nodules on the face and upper back, accompanied by sharp episodic pain on the face. He had undergone nephrectomy for renal cancer 9 years ago, and his younger brother had similar cutaneous manifestation. Histopathologic findings were consistent with pilar leiomyoma, showing bundles of smooth muscle tumors in the dermis. Based on the clinical information including clinical features, past medical history, and family history, HLRCC was highly suspected. To confirm the diagnosis, whole exome sequencing was performed using peripheral blood, which revealed a novel point mutation (c.739G>A, p.Glu247Lys) in the fumarate hydratase (FH) gene. We describe a confirmed case of HLRCC, which is a genetic disorder with a potential to cause visceral cancers, which dermatologists might overlook as a benign condition.

A Case Report of Rubinstein-Taybi Syndrome Presenting with Extensive Keloid Formation and Review of Literature.

Rubinstein-Taybi syndrome (RSTS) is an extremely rare genetic disorder affecting multi-organ systems. A tendency to form keloid is one of the common dermatologic manifestations. We describe a 23-year-old female presented with extensive keloids which developed spontaneously. She had typical facial features, broad thumbs, and dental defects, which were suspicious features of genetic syndrome. Direct sequencing for cyclic-AMP-regulated enhancer binding protein revealed a novel mutation. So far, 23 cases of RSTS have been reported in Korean literature. To the best of our knowledge, this is the first report in Korea to describe confirmed case of RSTS with extensive keloids as a chief manifestation.

Basal cell carcinoma of the scalp shows distinct features from the face in Asians.

Basal cell carcinoma (BCC) affecting different sites has been reported to have different clinicopathological features. In previous studies, the scalp was commonly classified to the head and neck region. However, the scalp has distinct characteristics from those of other parts of the skin. We retrospectively reviewed the medical records of patients who underwent surgical treatment for BCC. A total of 734 lesions were examined, and 13.2% originated from the scalp. The nodular type was the most common histologic subtype; however, the proportion of the superficial type was significantly higher than that of facial BCC (p < 0.001). Compared with facial BCC, younger age (p = 0.046) and larger tumor size (p < 0.001) were observed in scalp BCC. These characteristics were similar to those of truncal BCC in that they demonstrated a higher proportion of the superficial type (p < 0.001), younger age (p = 0.001), and larger tumor diameter (p < 0.001) compared with BCC in the head and neck region. Scalp BCC and truncal BCC were not significantly different in terms of age (p = 0.052) and tumor size (p = 0.230). In conclusion, despite the anatomical proximity, features of scalp BCC were similar to those of truncal lesions compared with facial lesions. Scalp BCC might be a separate entity from facial BCC.

Clinical characteristics of pustulotic arthro-osteitis in Korea.

Pustulotic arthro-osteitis (PAO) has been studied primarily in Japan. However, there is a lack of research regarding its clinical features among large populations in other countries and it is often believed to be similar to psoriatic arthritis (PsA). Although the association between psoriasis (PsO) and palmoplantar pustulosis (PPP) is debatable, differences in the clinical characteristics between PsA and PAO might support the notion that PsO and PPP are distinct entities. This study aimed to investigate the clinical characteristics of PAO in Korean patients and to compare them with those of PsA. We retrospectively reviewed the medical records of patients diagnosed with PPP, PAO, and PsA. Among 266 patients with PPP, 13.2% had PAO. Unlike Japanese patients with PAO, Korean patients had a relatively lower involvement of the chest wall. PAO patients demonstrated lower age of onset, higher proportion of females, and higher severity of cutaneous eruptions compared to PPP patients without PAO, but the differences were not statistically significant. Female predominance was prominent in PAO compared to PsA. Cutaneous eruptions occurred earlier than joint symptoms in 83.5% of the patients with PsA and in 42.9% of the patients with PAO. PAO involved axial joints more frequently compared to PsA, especially the chest wall and spine. PsA mainly involved the peripheral joints, especially the metacarpophalangeal joints and distal interphalangeal joints of the hands and feet. In conclusion, PAO and PsA exhibited different demographics and locations of joint involvement, supporting the notion that PPP and PsO are separate disorders. Many PAO patients presented with joint symptoms before the appearance of skin eruptions, underlining the important role of dermatologists in recognizing PAO among PPP patients. Physicians should be aware of the characteristics of PAO while treating patients with PPP.

Evaluating outcomes of pulsed dye laser therapy combined with intralesional triamcinolone injection after surgical removal of hypertrophic cesarean section scars.

BACKGROUND: Recently, pulsed dye laser (PDL) combined with triamcinolone intralesional injection (TAILI) has been introduced for surgical scar prevention. However, little is known about this procedure's effectiveness in preventing hypertrophic scar following surgical scar removal. OBJECTIVES: This study aimed to evaluate the outcome of early intervention using PDL combined with TAILI after surgical removal of hypertrophic cesarean section (CS) scars. METHODS: The medical records of 35 patients who underwent early intervention using PDL and TAILI after removal of hypertrophic CS scars were retrospectively reviewed. The scars' average Vancouver Scar Scale (VSS) scores before scar removal and 3 months after the final treatment were compared. RESULTS: The patients received 4.23 treatments on average and were followed up for a mean period of 7.74 months. The mean final VSS was 3.11 ± 1.52 and was significantly lower than that of the previous VSS (9.29 ± 1.74, p = 0.000). VSS of the previous CS scar, and the presence or absence of keloid formation in other areas, was associated with treatment outcome (p = 0.003 and 0.008, respectively). CONCLUSIONS: Early intervention using PDL combined with TAILI could prevent the recurrence or progression of hypertrophic CS scarring after surgical scar removal.

Myosin-VIIa is expressed in multiple isoforms and essential for tensioning the hair cell mechanotransduction complex.

Mutations in myosin-VIIa (MYO7A) cause Usher syndrome type 1, characterized by combined deafness and blindness. MYO7A is proposed to function as a motor that tensions the hair cell mechanotransduction (MET) complex, but conclusive evidence is lacking. Here we report that multiple MYO7A isoforms are expressed in the mouse cochlea. In mice with a specific deletion of the canonical isoform (Myo7a-ΔC mouse), MYO7A is severely diminished in inner hair cells (IHCs), while expression in outer hair cells is affected tonotopically. IHCs of Myo7a-ΔC mice undergo normal development, but exhibit reduced resting open probability and slowed onset of MET currents, consistent with MYO7A's proposed role in tensioning the tip link. Mature IHCs of Myo7a-ΔC mice degenerate over time, giving rise to progressive hearing loss. Taken together, our study reveals an unexpected isoform diversity of MYO7A expression in the cochlea and highlights MYO7A's essential role in tensioning the hair cell MET complex.

Association between Dietary Mineral Intake and Chronic Kidney Disease: The Health Examinees (HEXA) Study.

Few studies have explored the association between mineral intake and chronic kidney disease (CKD). A cross-sectional analysis investigated the association between mineral intake (calcium, phosphorus, sodium, potassium, iron, and zinc) and CKD using the Health Examinee (HEXA) cohort of the Korean Genome and Epidemiologic Study (KoGES). For 159,711 participants, mineral intake was assessed by a food frequency questionnaire. CKD was defined as an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m². Dietary intake of each mineral was divided into quartiles and the quartile including recommended dietary allowance (RDA) or adequate intake (AI) of each mineral was used as a reference. We assessed the association between the quartile of mineral intakes and CKD using polytomous logistic regression models. The lowest quartiles of phosphorus (≤663.68 mg/day, odds ratio [OR] = 1.64, 95% confidence interval [CI]: 1.25⁻2.15), potassium (≤1567.53 mg/day, OR = 1.87, 95% CI: 1.27⁻2.75), iron (≤6.93 mg/day, OR = 1.53, 95% CI: 1.17⁻2.01), and zinc (≤5.86 mg/day, OR = 1.52, 95% CI: 1.02⁻2.26) were associated with higher odds for advanced CKD compared with the references. The present study suggests that an inadequate intake of some minerals may be associated with CKD occurrence in the general population. Due to the reverse causation issue in this cross-sectional study design, further longitudinal prospective studies are needed in order to prove the results.

Rapid antibiotic susceptibility testing by tracking single cell growth in a microfluidic agarose channel system.

Sepsis is one of the major causes of death in the US, necessitating rapid treatment with proper antibiotics. Conventional systems for antibiotic susceptibility testing (AST) take far too long (16-24 h) for the timely treatment of sepsis. This is because they rely on measuring optical density, which relates to bacterial growth, to determine the minimal inhibitory concentrations (MICs) of relevant antibiotics. Thus, there is a desperate need for more improved and rapid AST (RAST) systems. The RAST system can also reduce the growing number of clinical problems that are associated with antibiotic resistance caused by methicillin-resistant Staphylococcus aureus, vancomycin-resistant Staphylococcus aureus, and vancomycin-resistant enterococci. In this study, we demonstrate a microfluidic agarose channel (MAC) system that reduces the AST assay time for determining MICs by single bacterial time lapse imaging. The MAC system immobilizes bacteria by using agarose in a microfluidic culture chamber so that single cell growth can be tracked by microscopy. Time lapse images of single bacterial cells under different antibiotic culture conditions were analyzed by image processing to determine MICs. Three standard bacteria from the Clinical and Laboratory Standard Institute (CLSI) were tested with several kinds of antibiotics. MIC values that were well matched with those of the CLSI were obtained within only 3-4 h. We expect that the MAC system can offer rapid diagnosis of sepsis and thus, more efficient and proper medication in the clinical setting.