Allele-specific CRISPR-Cas9 editing of dominant epidermolysis bullosa simplex in human epidermal stem cells.

Epidermolysis bullosa simplex (EBS) is a rare skin disease inherited mostly in an autosomal dominant manner. Patients display a skin fragility that leads to blisters and erosions caused by minor mechanical trauma. EBS phenotypic and genotypic variants are caused by genetic defects in intracellular proteins whose function is to provide the attachment of basal keratinocytes to the basement membrane zone and most EBS cases display mutations in keratin 5 (KRT5) and keratin 14 (KRT14) genes. Besides palliative treatments, there is still no long-lasting effective cure to correct the mutant gene and abolish the dominant negative effect of the pathogenic protein over its wild-type counterpart. Here, we propose a molecular strategy for EBS01 patient's keratinocytes carrying a monoallelic c.475/495del21 mutation in KRT14 exon 1. Through the CRISPR-Cas9 system, we perform a specific cleavage only on the mutant allele and restore a normal cellular phenotype and a correct intermediate filament network, without affecting the epidermal stem cell, referred to as holoclones, which play a crucial role in epidermal regeneration.

Mesenchymal stem cells for the treatment of psoriasis: a comprehensive review.

Mesenchymal stem cells (MSCs) have recently been shown to have not only regenerative capabilities but also immunomodulating properties. For this reason, they are currently under investigation in clinical trials for the treatment of several autoimmune systemic disorders. Psoriasis is a systemic immune-mediated disease for which MSCs could have therapeutic potential. We analysed the existing literature with regard to MSC-based strategies for the treatment of psoriasis, using the MEDLINE, Embase, Scopus and Cochrane Library electronic databases from inception to the date of study. A number of studies confirm the involvement of MSCs in psoriasis pathogenesis and therefore designate MSCs as an important potential therapeutic tool in this setting. Preclinical data are mostly based on imiquimod-induced murine models of psoriasis, and confirm the anti-inflammatory and immunomodulatory action of MSCs in the setting of psoriasis. Six patients affected by psoriasis were described in four clinical studies. Despite significant differences in terms of therapeutic protocols and clinical outcomes, the MSC-based regimens were efficacious in 100% of the cases. Despite more data still being needed, MSCs could be a promising therapy for psoriasis.

Favre-Racouchot disease: systematic review and possible therapeutic strategies.

Favre-Racouchot disease (FRD) is a relatively common dermatosis induced by chronic sun exposure. FRD is clinically and histologically characterized by the presence of both comedones and cysts in the context of an elastotic degeneration of the dermis. Those lesions are mainly located in the face, especially in the malar and periorbital areas. Smoking and radiotherapy seem to play a role in the pathogenesis together with UV exposure. The disease affects predominantly the aged population and seems to be a problem of mainly aesthetic concern. No official guidelines are available for the treatment of FRD; most common therapeutic strategies are represented by topical retinoids and laser treatments. The goal of our review was to identify the principal clinical and epidemiological characteristics of FRD and to analyse all the therapeutic strategies available. We also focused our attention on the follow-up of this particular dermatosis. Our aim was therefore to suggest alternative possible strategies for both the treatment and the follow-up of these patients. Our data support the efficacy of carbon dioxide laser and topical retinoids in the setting of FRD, but we also suggest considering alternative treatments, such as plasma exeresis. We also recommend planning both a short-term and a long-term follow-up visit, as the majority of relapses is observed after 10-12 months.

Maxillary sinus volume: new physiopathological data in fungal ball genesis? A retrospective study.

OBJECTIVES: The goal of this study was to compare maxillary sinus (MS) volume in patients with, or without, maxillary fungal ball. DESIGN: Monocentric retrospective study performed on 115 patient CT scans. SETTINGS: We defined two groups of patients according to the absence (control group) or the presence (fungal ball group) of unilateral fungal ball in the MS. Sinus 3D reconstruction was created from CT scan. PARTICIPANTS: Control group: 71 patients (36 women - 50.7%); mean age was 51 years. Fungal ball group: 44 patients (29 women - 65.9%); mean age was 54.5 years. MAIN OUTCOME MEASURE: The univariate association between MS volume and sinus covariates was tested by anova. Multivariate analysis was made including all variables statistically significant in univariate analysis. RESULTS: In the control group, mean MS volume was 14 766 mm3 . The volumes of the two MSs were not statistically different in the control group (P = 0.145). In the fungal ball group, mean MS volume was 15 982 mm3 . Fungal ball was found in the smallest MS in 41 of 44 cases. Univariate analysis showed a statistical difference between the pathological and the non-pathological MS volumes (P < 10-4 ). Multivariate analysis confirmed the correlation between MS volume and the presence of a fungal ball (P < 10-4 ). CONCLUSIONS: This study suggests that maxillary fungal ball is associated with a smaller size of the affected MS.

Lichen sclerosus of the oral mucosa: a hidden phenomenon.

Oral lichen sclerosus (OLS) represents a diagnostic challenge even for expert dermatologists due to its rarity and subtle clinical manifestations. Only few cases have been reported in literature to date. OLS typically presents with whitish macules in the oral cavity. Histopathological examination remains crucial for definitive diagnosis, with characteristic features including epithelial atrophy, subepithelial hyalinization, loss of elastic fibers, and lymphocytic infiltration. Management strategies vary depending on lesion size and symptomatic presentation, with topical or intralesional corticosteroids being the most commonly used treatment modalities. Long-term monitoring is recommended due to the potential for malignant transformation, although no cases have been reported to date. Greater awareness and understanding of OLS are essential for accurate diagnosis and effective management. Based on these findings, we recommend performing an accurate evaluation of the oral mucosa, especially when dealing with patients affected by genital or extragenital lichen sclerosus (LS). Moreover, we emphasize the importance of multidisciplinary collaboration between dermatologists and other specialists of oral disorders, such as dentists. This short review briefly summarizes available data on OLS, highlighting its diverse clinical presentations and diagnostic challenges. Despite its infrequent occurrence, OLS should be considered in the differential diagnosis of white macules in the oral cavity.

Maternal cardiac deceleration capacity: a novel insight into maternal autonomic function in pregnancies complicated by hypertensive disorders and intrauterine growth restriction.

OBJECTIVE: To explore maternal cardiac deceleration capacity (DC), a marker of autonomic function derived from electrocardiographic (ECG) signals, in pregnancies complicated by intrauterine growth restriction (IUGR) and hypertensive disorders of pregnancy (HDP) associated to IUGR (HDP-IUGR) or to appropriate for gestational age fetal growth (HDP-AGAf). METHODS: Prospective single center case-control study conducted at Buzzi Children's Hospital, Milan. Maternal ECGs were analyzed by Phase Rectified Signal Averaging (PRSA) method to obtain cardiac DC in women with: HDP-IUGR, HDP-AGAf, severe-IUGR, mild-IUGR and uncomplicated pregnancies. IUGR was defined as abdominal circumference <5th centile; severe-IUGR was associated with umbilical artery Doppler pulsatility index >2 standard deviations. Non-parametric tests were adopted. RESULTS: 269 women were recruited. Women with HDP-IUGR (n=35) showed significantly higher cardiac DC compared both to controls (n=141) (p=0.003) and women with HDP-AGAf (n=18) (p=0.01). Women with severe-IUGR (n=14) showed significantly higher DC than controls (p=0.01). Women with mild-IUGR (n=61) as well as women with HDP-AGAf showed no differences in DC compared to controls (both p=0.3). CONCLUSIONS: Women with pregnancy complicated by severe placental failure, such as HDP-IUGR and severe IUGR, show significant autonomic alterations, as indicated by elevated cardiac DC. On the contrary, pregnancy complications such as HDP-AGAf and mild IUGR show no impact on maternal autonomic balance. We present a new approach to explore maternal autonomic cardiovascular regulation that might reflect the severity of placental vascular insufficiency.

The Alzheimer-related gene presenilin-1 facilitates sonic hedgehog expression in Xenopus primary neurogenesis.

We analyzed the influence of presenilins on the genetic cascades that control neuronal differentiation in Xenopus embryos. Resembling sonic hedgehog (shh) overexpression, presenilin mRNA injection reduced the number of N-tubulin+ primary neurons and modulated Gli3 and Zic2 according to their roles in activating and repressing primary neurogenesis, respectively. Presenilin increased shh expression within its normal domain, mainly in the floor plate, whereas an antisense X-presenilin-alpha morpholino oligonucleotide reduced shh expression. Both shh and presenilin promoted cell proliferation and apoptosis, but the effects of shh were widely distributed, while those resulting from presenilin injection coincided with the range of shh signaling. We suggest that presenilin may modulate primary neurogenesis, proliferation, and apoptosis in the neural plate, through the enhancement of shh signaling.

Intestinal surgery in patients with ovarian carcinoma.

Twenty patients affected with ovarian carcinoma underwent intestinal operations between 1979 and 1987 during the course of the disease. The patients were divided into two groups on the basis of the time and the aim of the adopted surgery. The first group had intestinal surgery during the initial laparotomy for debulking of the tumour and amelioration of bowel function, while the patients of the second group underwent re-exploration at different times from the first laparotomy for symptomatic intestinal involvement by tumour, with the aim of palliation for obstruction. In all the cases the intestinal obstruction, complete or incomplete, was caused by tumoral involvement of the loops histologically proven. The patients were affected with ovarian carcinoma at stage III (80%) and IV (20%) FIGO. The survival at the intestinal surgery, correlated to the FIGO stage and the kind of surgery performed are presented.

A comparison of droperidol and metoclopramide in the treatment of nausea and vomiting during cis-platinum polichemotherapy in ovarian carcinoma.

A comparison was made of the anti-emetic effects of Droperidol (total dose: 5 mg e.v.) and Metoclopramide (total dose: 30 mg e.v.), on 7 patients affected by advanced ovarian carcinoma and undergoing polychemotherapeutical treatment with courses including 50 mg/mq-doses of Cis-Dichlorodiaminoplatinum (DDP). Although no significant difference was observed between the emetic-control effects of the two substances, Droperidol was preferred by all patients, owing to its subjective effects.

Sonographic morphology of the endometrial hyperplasia.

Echographic appearances of the uterus of 56 women for whom the ultrasound diagnosis was suggestive of endometrial hyperplasia have been examined.

[The biochemical screening of Down's syndrome]. / Screening biochimico della sindrome di Down.

Since the initial observation of an association between low maternal serum aFP and trisomies noninvasive for chromosomal abnormalities is an obvious goal of genetics and obstetricians. Here are reported the results of a biochemical screening for fetal trisomies study based on the dosages of maternal serum aFP, bHCG and uE3 at 16 week gestational age on 1166 pregnant women without risk factors for genetical abnormalities. Sensitivity, positive predictivity and negative predictivity of the screening were 50%, 42.86% and 99.74% respectively.

Serial detection of plasma-factor XIII levels during the ovulatory cycle and estroprogestative contraception.

PIP: The authors examine the variations of plasma factor 13 (PF13) levels during the physiological cycle and estroprogestative contraception. Blood samples were taken from 8 women aged 21-26 who had used a combined estroprogestative oral contraceptive (OC), ethinyl estradiol 0.003 mg, levonorgestrel 0.15 mg, and from 10 healthy women aged 23-29, normally ovulating. Each subject underwent 4 venopunctures during the same month. The detection of PF13 levels from the 10 normally ovulating women resulting in the following mean values were found: 1) proliferative phase, day 6-10, 92%; 2) periovulatory phase, day 13-15, 67.2%; 3) secretive phase, days 20-23, 85%; and 4) premenstrual phase, day 27-29, 89.4%. There was a highly significant decrease of PF13 during periovulatory phase when compared with the other phases (p0.001). The detection of PF13 levels for the 8 women using OCs was: 1) end of 1st week from bleeding, day 7-8, 112.5%; 2) end of 2nd week, days 13-15, 113.1%; 3) end of 3rd week, days 20-22, 113.1%; and 4) end of 4th week, days 27-29, 113.1%; for the latter group no significant differences were found. The mean values resulted higher for the women using OCs in every serial sample. These results suggest a possible action of steroid hormones on PF13 levels and through it on the last step of coagulation process, the fibrinostabilization.^ieng

A Case of Abruptio Placentae due to the Torsion of Gravid Uterus.

Torsion of a gravid uterus is a rare obstetric emergency potentially lethal for the fetus and the mother. Some of the cases described in literature are associated with preexisting gynecologic conditions related to pelvic and uterine anatomy, even if most of cases remain unexplained. We report a case of acute 180-degree torsion of uterus at 33 weeks of gestation associated with abruptio placentae in a young Asian woman without apparent risk factors.

Cesarean section plus delayed cord clamping approach in the perinatal management of congenital high airway obstruction syndrome (CHAOS): a case report.

In this case, we describe a newborn with prenatal diagnosis of congenital high airway obstruction syndrome (CHAOS), successfully managed with a cesarean section with delayed cord clamping 180 seconds. In case of prenatal diagnosis of CHAOS, prompt airway intervention at delivery allows survival of this otherwise fatal condition. Ex utero intrapartum treatment (EXIT) is considered the elective procedure to secure the fetal airway before the baby is completely separated from the maternal circulation. In cases where the EXIT procedure is not possible for maternal reasons (Ballantyne's syndrome), delayed cord clamping may serve as an alternative method to manage CHAOS.

How to replace codeine after tonsillectomy in children under 12 years of age? Guidelines of the French Oto-Rhino-Laryngology--Head and Neck Surgery Society (SFORL).

The authors present the guidelines of the French Oto-rhino-laryngology--Head and Neck Surgery Society (SFORL) regarding pain management in children and adults following tonsillectomy. A multidisciplinary work group was entrusted with a literature review. Guidelines were drawn up based on the articles retrieved and the group members' experience. They were read over by an editorial group independent of the work group. A coordination meeting drew up the final version. Guidelines were graded A, B or C or as professional agreement in decreasing order of level of evidence. At home, non-steroid anti-inflammatory drugs (NSAIDs) are recommended in association with paracetamol in elevated respiratory risk and especially obstructive sleep apnea syndrome; in elevated hemorrhagic risk (hemostasis disorder, surgical problems, etc.), tramadol is recommended. Two other treatment schedules (modified NSAIDs and corticosteroids) have not undergone dedicated study and should be assessed. Management of post-tonsillectomy pain in children is founded on individual risk/benefit analysis.