Neuroplacentology is an expanding field of interest that addresses the placental influence on fetal and neonatal brain lesions and on further neurodevelopment. The objective of this study was to clarify the link between placental pathology and perinatal arterial ischemic stroke (PAIS). Prior publications have reported different types of perinatal stroke with diverse methodologies precluding firm conclusions. We report here the histological placental findings in a series of 16 neonates with radiologically confirmed PAIS. Findings were grouped into 3 categories of lesions: (1) inflammation, (2) placental and fetal hypoxic lesions, and (3) placentas with a high birthweight/placenta weight ratio. Matched control placentas were compared to the pathological placentas when feasible. The eight term singleton placentas were compared to a series of 20 placentas from a highly controlled amniotic membrane donation program; in three twin pregnancies, the placental portions from the affected twin and unaffected co-twin were compared. Slightly more than half (9/16, 56%) had histopathological features belonging to more than one category, a feature shared by the singleton control placentas (13/20, 65%). More severe and extensive lesions were however observed in the pathological placentas. One case occurring in the context of SARS-CoV-2 placentitis further expands the spectrum of COVID-related perinatal disease. Our study supports the assumption that PAIS can result from various combinations and interplay of maternal and fetal factors and confirms the value of placenta examination. Yet, placental findings must be interpreted with caution given their prevalence in well-designed controls.

BACKGROUND: Commonly reported symptoms of long COVID may have different patterns of prevalence and presentation across different countries. While some limited data have been reported for the United Kingdom, national specificity for Scotland is less clear. We present a cross-sectional survey to examine the symptom prevalence, frequency, and severity of long COVID for people living with the condition in Scotland.
METHODS: An online survey was created in the English language and was available between April 21, 2022 and August 5, 2022. Participants were included if they were ≥18 years old, living in Scotland, and had self-diagnosed or confirmed long COVID; and excluded if they were hospitalized during their initial infection. Within this article we quantify symptom prevalence, frequency, severity, and duration.
RESULTS: Participants (n = 253) reported the most prevalent long-COVID symptoms to be post-exertional malaise (95%), fatigue/tiredness (85%), and cognitive impairment (68%). Fatigue/tiredness, problems with activities of daily living (ADL), and general pain were most frequently occurring, while sleep difficulties, problems with ADL, and nausea were the most severe. Scottish Index of Multiple Deprivation associated with symptom number, severity, and frequency, whereas vaccine status, age, sex, and smoking status had limited or no association.
CONCLUSIONS: These findings outline the challenges faced for those living with long COVID and highlight the need for longitudinal research to ascertain a better understanding of the condition and its longer-term societal impact.

It is challenging to establish animal models to mimic perinatal arterial ischemic stroke. Here, we provided two approaches that precisely occlude rodent pups\' distal middle cerebral artery of rodent pups at any postnatal age. One uses magnetic nanoparticles to generate platelet-rich thrombus, and the other utilizes magnetized red blood cells (mRBCs) to generate an erythrocyte-rich embolus. Both approaches result in focal cerebral ischemia followed by controllable reperfusion while requiring no arterial surgery.

Complete Androgen Insensitivity Syndrome (CAIS) is a rare genetic condition by mutations in the androgen receptor (AR) gene resulting in target issue resistance to androgens and a female phenotype in genetically male individuals. A 16-year-old phenotypically female individual presented to our clinic with primary amenorrhea. Her clinical evaluation showed normal female external genitalia, Tanner III breast development and sparse pubic and axillary hair (Tanner stage II). Hormonal assessment revealed increased concentrations of Luteinizing Hormone (LH), Testosterone and Antimüllerian Hormone (AMH). Image studies detected no uterus or gonads, but a blind vagina and the karyotype was 46, XY. These findings suggested the diagnosis of CAIS, and genetic testing of the AR gene revealed a rare pathogenic mutation of cytosine to adenine (c.2612C>A) replacing alanine with glutamic acid at position 871 (p.Ala871Glu) in the AR, previously described once in two adult sisters. The patient underwent gonadectomy and received hormonal replacement therapy. This study expands the AR mutation database and shows the complexity and the importance of prompt diagnosis, proper management, and follow-up for CAIS patients, underlining the need for standardized protocols.

BACKGROUND: Posterior ankle impingement syndrome (PAIS) may result from flexor hallucis longus tendinopathy, compression of the posterior process of the talus from the presence of an os trigonum, soft-tissue impingement, or a combination of these. Posterior extra-articular endoscopy performed with the patient supine through the double posteromedial portals, with excision of adhesions, excision of the posterior process of the talus or an os trigonum, and decompression of the tendon of the flexor hallucis longus (FHL), can be used in athletes with PAIS.
METHODS: Thirty-four athletes with PAIS in whom conservative management had failed underwent posterior ankle endoscopy in the supine position using the double posteromedial portals. The patients were assessed pre- and postoperatively using the American Orthopaedic Foot and Ankle Society hindfoot scale score, the Tegner scale, and the simple visual analogue scale. Time of surgery, return to sports, patient satisfaction, and complications were recorded and analysed. The average length of postoperative follow-up was 26.7 ± 12.6 (range 24 to 72) months.
RESULTS: The mean Tegner activity scale score improved to 9 ± 0.2 postoperatively (p < 0.05), while the mean American Orthopaedic Foot and Ankle Society scale score improved to 96 ± 5.1 (range 87 to 100) postoperatively, with 29 of 34 patients (85.3%) achieving a perfect score of 100 (p < 0.05). The mean time to return to sports was 8.7 ± 0.7 (range 8 to 10) weeks. The complication rate was low, with no superficial wound infections or venous thromboembolism events; only two patients (5.9%) reported pain and tenderness by 3 months after the index procedure.
CONCLUSIONS: Posterior ankle endoscopy for the resection of a posterior process of the talus or an os trigonum and decompression of the tendon of FHL is safe and allows excellent outcomes with low morbidity in athletes with PAIS.

The aim of the current study was to adapt and validate the Prejudice Against Immigrants Scale (PAIS) in the Italian context, based on the Prejudice Against Asylum Seekers Scale by Anderson (2018). The validity, reliability, and measurement invariance across gender, age, and educational levels of the scale were assessed through three sources, which involved 306 Italian individuals (N men = 151, 49.3%) between 18 and 60 years old. Both exploratory and confirmatory factor analyses (CFA) confirmed the two-factor solution of the original instrument by excluding two items, which were present in the previous validation study. The first factor is classical prejudice against immigrants, which maps onto theoretical derivations of classical and old-fashioned prejudices, whereas the second factor is conditional prejudice against immigrants, which maps onto theoretical derivations of subtle and modern prejudices. Findings of the multigroup CFAs demonstrated full configural and metric invariance and partial scalar invariance of the scale across gender, age, and educational level. The analyses confirmed that PAIS has high levels of reliability and criterion and construct validity, showing findings that are comparable to those of Anderson (2018). These results suggest that PAIS presents very good psychometric properties and could be considered a valid and reliable instrument to measure prejudice against immigrants, by enabling Italian researchers to detect both covert and more subtle forms of prejudice against immigrants. Limitations and further directions are discussed.

OBJECTIVE: To verify whether early intervention focused on the family improves the cognitive, motor, and language development of children born preterm and/or at social risk in the first 3 years of life.
METHODS: Meta-analysis of clinical trials published between 2008 and 2018, in the following databases: CINAHL, MEDLINE - PubMed, MEDLINE - BVS, LILACS - BVS, IBECS - BVS, PEDro and Cochrane Reviews. Experimental studies on early interventions focused on the family, whose target groups were children born preterm and/or at social risk, with assessment of cognitive and/or motor and/or language development up to 3 years were included. The studies were rated using the PEDro Scale.
RESULTS: Twelve studies were included from a total of 3378 articles. Early intervention focused on the family contributed to the development of the cognitive (Standardized Mean Difference - SMD=0.48, 95% CI: 0.34-0.61) and motor (SMD=0.76, 95% CI: 0.55-0.96) domains of preterm infants. Regarding cognitive development, performance improvement was observed at 12, 24 and 36 months, while in the motor domain, the effect was observed only at 12 months in preterm infants. There was no benefit of the intervention in the cognitive, motor, and language outcomes of children with the social risk factor associated to biological risk.
CONCLUSIONS: Early intervention focused on the family has a positive effect on the cognition of preterm infants. The effect on motor development was lower, possibly due to the emphasis on interventions in family-child interaction. The effect of interventions on the development of children at social risk and on the language domain was inconclusive, due to the scarcity of studies in the area.

OBJECTIVE: To perform a systematic review with meta-analysis and meta-regression to correlate the total scores of asthma control with the increase in the total scores of health-related quality of life levels of parents of asthmatic children.
METHODS: The search was carried out in the following databases: PubMed (MEDLINE); Embase and ScienceDirect (Elsevier); SciELO and LILACs (Bireme) in June 2017. The included studies assessed asthma control through the Asthma Control Questionnaire (ACQ), Asthma Control Test (C-ACT/ACT), and Global Initiative for Asthma (GINA) questionnaires, whereas the Pediatric Asthma Caregiver\'s Quality of Life Questionnaire (PACQLQ) was applied to assess the HRQoL of parents and family members.
RESULTS: 294 articles were evaluated in the selected databases, of which (n=38) were excluded for duplicity; (n=239) after the reading of the titles and abstracts and (n=5) after reading the studies in full, totaling 12 studies eligible for the meta-analysis. Of the 12 eligible articles, 11 (92%) were published in the last five years, and evaluated children and adolescents aged 1-20 years, totaling 2804 samples. In the evaluation of the correlation between the disease control scores by ACQ and C-ACT/ACT, the results were satisfactory for both ACQ analyses [R2: -0.88; p<0.001], and for C-ACT/ACT [R2: 0.82; p<0.001].
CONCLUSIONS: The results show that asthma control levels can influence the total HRQoL scores of parents or relatives of children and adolescents with asthma.

BACKGROUND: The Dallas Reifenstein family - first described in 1965 - includes 14 known members with partial androgen insensitivity syndrome (PAIS). However, the underlying molecular defect was never identified.
OBJECTIVE: To identify the underlying genetic defect for PAIS in the Dallas Reifenstein family.
METHODS: DNA was purified from scrotal skin fibroblasts, and whole exome sequencing was then performed in four affected men in the family. Additional family members - both affected and unaffected - were subsequently recruited to confirm segregation of the candidate mutations with the PAIS phenotype.
METHODS: The affected men have PAIS with infertility associated with azoospermia, hypospadias, and gynecomastia.
RESULTS: All four men harbored an intronic variant NC_000023.10:g.66788676A>C between exon 1 and exon 2 of the androgen receptor (AR) canonical transcript NM_000044 (complementary DNA position NM_000044: c.1616+22072A>C) predicted to cause an alternatively spliced AR transcript. Reverse transcription (RT) polymerase chain (PCR) experiments detected the predicted PCR product of the alternatively spliced AR transcript, and the mutation segregated with the PAIS phenotype in this family. The transcript includes the insertion of 185 nucleotides with a premature stop codon at chrX:66863131-66863133, likely resulting in a reduction in AR protein expression due to nonsense-mediated decay.
CONCLUSIONS: An intronic AR mutation was identified in the Dallas Reifenstein family. The findings suggest that in cases of PAIS without identifiable AR mutations in coding regions, intronic AR mutations should be considered.

Androgen insensitivity syndrome (AIS) is an X-linked disorder caused by mutations in the NR3C4 gene, which encodes the androgen receptor (AR). In this study, we performed mutational analyses to identify AR molecular defects, in individuals with 46,XY disorders of sex development (46,XY DSD) and a presumptive diagnosis of AIS. Eighteen different gene mutations, including seven previously unreported new variants, were detected in 26 unrelated cases. These included two deletion mutations (P49fs*185 and E308f*320) in exon 1 and five substitution mutations (p.S792P, p.D829G, p.R832P, p.L839F, and p.K906E) located in the steroid-binding domain. Expression analyses of mutants generated by site-directed mutagenesis indicated that these new gene variants impaired AR function by affecting its binding activity. Seventeen of 18 mutations likely lead to reduced or absent responses to androgens, which may in turn account for the different degrees of undermasculinization observed. Our study provides insight into the functional consequences of these mutations.