Cytomegalovirus (CMV) is the most common congenital and perinatal viral infection. It can occur in utero, during delivery, by blood transfusion or by breast milk. These are usually asymptomatic in term infants due to the presence of maternally derived, trans placental CMV (Ig)G antibodies, but in premature neonates, can lead to severe disease because of lack of sufficient quantities of these antibodies 1. In lactating CMV seropositive mothers, transmission occurs in 22.8% premature infants, with symptomatic disease in 34.5%. 2 We report 3 cases of neonates with atypical CMV infection involving lungs and requiring treatment with antivirals.

Background. Anaphylaxis is a severe and potentially life-threatening allergic reaction which has a detrimental impact on quality of life (QoL), however little is known about the impact of anaphylaxis, across the various causes, on adults. The aim of this study was to assess the impact of anaphylaxis on QoL and mental health in adults. Methods. Participants (n=142; 60% female) were recruited from a regional allergy centre (Birmingham, U.K) following systematic specialist evaluation. They completed measures of generic QoL (WHOQoL BREF), anaphylaxis specific QoL (A-QoL-Adults), anxiety and depression (HADS) and stress (PSS). Results. Anaphylaxis triggers were mainly to medication or during general anaesthesia (29.6%), food (29.6%), wasp or bee venom (16.2%), or were spontaneous (21.1%). Adults with anaphylaxis had significantly poorer general QoL and stress than published data from a healthy population. Females had significantly poorer anxiety and depression than norm data (all p<0.01). Poorer anaphylaxis specific QoL was significantly related to greater stress, depression, anxiety, poorer general QoL and demographic and clinical variables such as age, gender, severity of anaphylaxis, presence of other atopic conditions (all p<0.05). Regression analysis showed that anxiety, depression and number of anaphylactic reactions were significant predictors for anaphylaxis specific QoL. Conclusions. Anaphylaxis has an adverse impact on QoL and mental health of adults across different triggers. Anxiety, depression and number of reactions in particular seem to be important in explaining the impact on QoL and should be of particular note for clinicians managing adults with this condition, and when considering specialist psychological support.

Background Cystic Fibrosis (CF) and autism spectrum disorder (ASD) are life-long conditions with intense treatment burdens for patients and families. Patients with a concurrent diagnosis (CF-ASD) experience unique challenges to CF care. This study describes the experiences of our multidisciplinary CF team in caring for patients with CF-ASD and provides insight into provider and parental perspectives on clinical management. Methods This is a three-part IRB-approved study involving 1) retrospective chart review of patients with CF-ASD, 2) qualitative interviews with multi-disciplinary care teams, and 3) qualitative interviews with caregivers of patients with CF-ASD. Challenges in clinical management of this specific cohort were compiled using data from chart review and care team interviews. Strategies to address these challenges were identified and rated by individual families based on relevance and practicality. Results Within our CF center, 12 patients have an official diagnosis of ASD. Median age of patients with CF-ASD was 8.5 years (range 3-20 years), 75% were male, and 83% were on highly effective modulator therapy. Clinical challenges included sensory processing issues, environmental overstimulation, intolerance to procedures and disrupted routines. Potentially impactful strategies include patient-specific coping plans, guided behavioral interventions, parental advocacy, and improved communication between the family and multidisciplinary team. Conclusions Children with CF-ASD face extraordinary challenges beyond the experience of neurotypical children with CF. Increased awareness of this complex dual diagnosis will help providers be sensitive to the unique needs of these patients, to help build consistent and trustworthy relationships with families, and to provide effective clinical care despite limitations.

Abstract Objective: To investigate serum human epididymis-4 (HE4) as a predictive biomarker of intrauterine progestin response in endometrial cancer and atypical endometrial hyperplasia (AEH). Design: Prospective observational study. Setting: Consecutive sample of women attending a tertiary gynaecological oncology centre in the North West of England. Population: Women with AEH or early stage, low grade endometrial cancer who were unfit or declined primary surgical management; 48 in the discovery cohort and 28 in the validation cohort. Methods: Women were treated with a levonorgestrel intrauterine system (LNG-IUS) for 12 months. Endometrial biopsies and imaging were performed to assess treatment response. Pre-treatment serum HE4 was analysed by chemiluminescence immunoassay and diagnostic accuracy and logistic regression analyses performed. Main outcome measure: Progestin response at 12 months defined by histology and imaging. Results: Baseline serum HE4 was significantly higher in non-responders than responders in both discovery [134.6pmol/L (IQR:94.0-292.4) vs 76.5pmol/L (IQR:59.7-87.3), p<0.001] and validation cohorts [108.2pmol/L (IQR:80.3-119.2) vs 64.4pmol/L (IQR:53.0-73.0), p=0.004]. An HE4≥77pmol/L had a sensitivity and specificity for progestin treatment response of 83.3% and 53.3% in the discovery cohort, and 85.7% and 76.2% and in the validation cohort, respectively. When expressed as a continuous variable, the AUC was 0.81 (95%CI:0.67-0.95) and 0.87 (95%CI:0.73-1.00) for the discovery and validation cohorts, with every 1pmol/L of HE4 increasing the likelihood of progestin treatment failure by 2% and 5%, after adjustment for age and histology, respectively (p=0.02 and p=0.18). Conclusion: Serum HE4 shows promise as a predictive biomarker of progestin treatment response in endometrial cancer and AEH.

Study Objective: Development of a prediction tool for histopathological adenomyosis diagnosis after hysterectomy based on MRI and clinical parameters. Design: Single-centre retrospective cohort study Setting: Gynaecological department of a referral hospital from 2007-2022. Population: 296 women undergoing hysterectomy with preoperative pelvic MRI Methods: MRI’s were retrospectively assessed for adenomyosis markers (junctional zone (JZ) parameters, high signal intensity foci (HSI) foci) in a blinded fashion. A multivariate regression model for histopathological adenomyosis diagnosis was developed based on MRI and clinical variables from univariate analysis with p>0.10 and factors deemed clinically relevant. Results: 131/296 women (44.3%) had histopathological adenomyosis. Patients were of comparable age at hysterectomy, BMI and clinical symptoms, p>0.05. Adenomyosis patients more often had undergone a curettage (22.1% vs. 8.9%, p=0.002), a higher mean JZ thickness (9.40 vs. 8.35mm, p <.001), maximal JZ thickness (16.00 vs. 13.40mm, p<.001), mean JZ/myometrium ratio (0.56 vs. 0.49, p=.040), and JZ differential (8.60 vs. 8.15mm, p=.003). Presence of HSI foci was a strong predictor for adenomyosis (39.7% vs. 8.9%, p<.001). Based on the parameters age and BMI, history of curettage, dysmenorrhoea, abnormal uterine bleeding (AUB), mean JZ, JZ Differential  5mm, JZ/myometrium ratio >.40, and presence of HSI Foci, a predictive model was created with a good Area Under the Curve (AUC) of .776. Conclusions: This is the first study to create a diagnostic tool based on MRI and clinical parameters for adenomyosis diagnosis. After sufficient external validation, this model could function as a useful clinical-decision making tool in women with suspected adenomyosis.

Rationale: Cystic Fibrosis (CF) newborn screening (NBS) algorithms in the USA vary by state. Differences in CF NBS algorithms could potentially affect the detection rate of CF newborns and lead to disparities in CF diagnosis amongst different racial and ethnic groups. Objectives: Generate a database of CF NBS algorithms in the USA and identify processes that may potentially lead to missed diagnoses or lead to health care disparities. Methods: We sent an online survey to state and regional CF and NBS leaders about the type and threshold of immunoreactive trypsinogen (IRT) cutoff used and methods used for CFTR gene variant analysis. Follow-up by email and phone was done to ensure a response from every state, clarify responses, and resolve discordances . Results: There was wide variation in the NBS algorithms employed by different states. Approximately half the states use a floating IRT cutoff and half use a fixed IRT cutoff. CFTR variant analysis also varied widely, with 2 states analyzing only for the F508del variant and 4 states incorporating CFTR gene sequencing. The other states used CFTR variant panels ranging from 23 to 365 CFTR variants. Conclusions: CF NBS algorithms vary widely amongst the different states in the USA, which affects the ability of CF NBS to diagnose newborn infants with CF consistently and uniformly across the country and potentially may miss more infants with CF from minority populations. Our results identify an important area for quality improvement in CF NBS.

Although COP is idiopathic by definition, it is important to investigate each diagnosed case for potential causes, such as iatrogenic from radiation or known causative medications [1], connective tissue diseases, inflammatory bowel disease, malignancies, history of lung transplant or bone marrow graft. OP may present weeks to months before other signs of connective tissue disorders and therefore the patient should undergo serologic testing for these diseases. [6] In the case presented, the specific etiology was unyielding and so remains cryptogenic in nature. This patient’s symptoms quickly improved following the use of steroids and tolerated tapering off completely without relapse one year out from initial diagnosis.

Objective: To assess the impact of an oocyte retrieval simulation training program (ORSTP) on the clinical performance of residents. Design: Prospective comparative study. Setting: A tertiary care center. Population: All OR performed by residents between May 2017 and November 2020. Methods & main outcome measures: The Simulation (S) group included OR performed by residents who had undergone an ORSTP before performing them on patients (n=422) and the control (C) group included OR performed by residents who had not received prior simulation training (n= 329). Our main outcome measure was the OR rate (ORR) (number of oocytes collected/number of follicles aspirated) during the first 3 months of the rotation. Results: In the S group, 6 residents aspirated 657 ovaries while in the C group, 5 residents aspirated 508 ovaries. The mean ORR during the first 3 months of rotation were comparable between the S and C groups (59% vs 58%). ORR during the first and second month, and at the end of the rotation were also comparable between the S and C groups (54% vs 63%, 58% vs 59% et 58% vs 58%, respectively). There was no significant difference in the rate of failed OR (3.3% vs 1.8%) between the S and C groups. Finally, 16% of residents in the S group reported being stressed before their first OR compared to 40% in the C group. Conclusions: The ORSTP does not improve the residents’ clinical performance, but it could decrease their stress in clinical practice.

Mini Commentary on manuscript ID BJOG-22-0531.R1

Domperidone is not a prescription drug in Pakistan and is available as an over-the-counter drug. This editorial shed light on the importance of clinicians' and patients' awareness of the adverse events associated with Domperidone use.

Camellia drupifera is a main tea-oil Camellia species, and understanding its genetic variation, origin and evolution will facilitate protection and utilization of its genetic resources. However, the differentiation, genetic variation, origin and evolution of C. drupifera remains unknown. Here, SRAP markers and chloroplast sequences of 32 C. drupifera populations were used to determine genetic variation and differentiation and infer the origin and evolutionary history of the species. Genetic diversity is low (H=0.200, Hd=0.861, Pi=0.00238), with obvious pedigree geographical structure among populations (Nst=0.612, Gst=0.117). Genetic differentiation is high (Gst=0.400, SRAP; Fst=0.68080, cpDNA), but gene exchange is low (Nm = 0.749 for nrDNA, Nm = 0.358 for cpDNA). The phylogenetic tree and PCA showed that this differentiation is mainly due to separation of the Hainan Island and mainland populations. Geographical isolation and island effects caused the pedigree structure, with large genetic differentiation, and reduced genetic diversity. STRUCTURE analysis revealed that compared with the Hainan Island population, the mainland population has a single genetic background. The TCS network showed that H17 was the original haplotype on Hainan Island; the H41 haplotype was important in the expansion of C. drupifera from Hainan Island to mainland China. Haplotype historical dynamics revealed expansion of the Hainan Island populations (Tajima’s D=-2.31467**, Fu’s Fs=-2.45270*). Comprehensive analysis suggests that C. drupifera originated on Hainan Island and expanded its range to mainland China. These results provide a scientific basis for the protection, development and utilization of C. drupifera resources and a good example of how geographic isolation and island effects can drive plant lineage differentiation.

We consider a mass conservative type method for semiconductor device problem by employing mixed finite element method (FEM) for electric potential equation, mass conservative characteristic FEM for both electron and hole density equations. The boundedness of numerical solution without certain time step restriction and optimal L^2 error estimates of full discrete scheme are proved. Numerical experiment is presented to verify the effectiveness and unconditional stability of the proposed method.

We study the large time behavior of solutions to the semilinear wave equation with space-dependent damping and absorbing nonlinearity in the whole space or exterior domains. Our result shows how the amplitude of the damping coefficient, the power of the nonlinearity, and the decay rate of the initial data at the spatial infinity determine the decay rates of the energy and the $L^2$-norm of the solution. In Appendix, we also give a survey of basic results on the local and global existence of solutions and the properties of weight functions used in the energy method.

A minority of neurologists is convinced that the disease "dementia praecox" first described by Emil Kraepelin in 1899 is still valid and its annexation by psychoanalysis and later by psychiatry has caused severe damage. The psychoanalytic extremist Eugen Bleuler had successfully annexed all conceivable mental conditions for Freud's couch therapy and had withdrawn them from medical research by his own postulates, which could never be proven. A recent further study now supports Kraepelin's once discarded thesis in a new way. This gives rise to a commentary by physicians on the clinical front.

Background and Purpose: Phosphodiesterases (PDEs) are a family of enzymes, which hydrolyze cAMP and cGMP. PDE10A is expressed mainly in the medium spiny neurons of the striatum that provides an opportunity to modulate the movement control pathways of the basal ganglia: “direct” (D1 receptor-dependent) and “indirect” (D2 receptor-dependent). Thus, inhibition of PDE10A can functionally mimic the action of both D1 receptor agonists and D2 receptor antagonists, although much less attention has been paid to the assessment of D1 receptor agonist-like effects. The purpose of the present study was (1) to confirm the motor stimulatory effects of PDE10A inhibitors and (2) to test whether these effects are subject to the development of tolerance. Experimental Approach: The ability of single or repeated (5 or 10 days) administration of selective PDE10A inhibitors, MP-10 (0,3-5 mg/kg) and RO5545965 (0.1-0.9 mg/kg), to stimulate locomotor activity was assessed in rats after single tetrabenazine challenge (3 mg/kg). The study was pre-registered on PreclinicalTrials.eu. Key Results: PDE-10A inhibition exerted paradoxical motor stimulatory properties in a dose-dependent manner. However, repeated administration of PDE10A inhibitors led to a reduction of their effects. Conclusion and Implications: PDE-10A inhibition produces a paradoxical increase in motor activity in animals with low dopamine tone. After repeated administration of PDE-10A inhibitors, these effects disappeared. The development of tolerance similar to that previously observed for D1-receptor agonists may limit the potential clinical use of the stimulatory effects of PDE10A inhibitors. Further studies aimed at analyzing the molecular mechanisms of this tolerance are warrant

Objective: the exact link between COVID-19 pandemic and different adverse outcomes of pregnancy remains unclear. Plus, large-scale research is lacking. In the present study, we aimed to compare the maternal and fetal health outcomes during the COVID-19 pandemic with the same last year duration in Iran. Design: Two retrospective cohorts (pre-COVID-19 and during COVID-19) were studied. The pre-COVID-19 cohort include pregnant women who had given birth between 1 January 2019 and 31 December 2019. The COVID-19 cohort, who had given birth between 1 January 2020 and 31 December 2020. The characteristics of pregnant women before COVID-19 and during COVID-19 pandemic were compared with Fisher’s exact test. Uni-variate and multivariate log-binomial regression models were used to determine the risk ratios of the impacts of the COVID-19 pandemic on adverse pregnancy outcomes. Results: among 128968 women showed that women who had given birth during the pandemic were more likely to be of young age, lower rates of alcohol consumption and smoking, lower weight gain, and higher rates of using synthetic milk for feeding neonates (P<0.05). Also, the risks of preterm labor were high (cOR 95% CI, 1.13 to 1.31; p<0.01) and the risk of caesarian were low (cOR 95% CI, 0.95 0.92 to 0.98; p<0.01) among pregnant women who gave birth during the COVID-19 pandemic compared with those who gave birth before the pandemic. Conclusions: In summary, we found that during the COVID-19 pandemic there were the higher risks of preterm labor and lower risk of caesarean among pregnant women.

Objectives: Nasopharyngeal (NP) depth prediction is clinically relevant in performing medical procedures, and enhancing technique precision and safety for patients. Nonetheless, clinical predictive variables and normative data in adults remain limited. This study aimed to determine normative data on NP depth and its correlation to external facial measurements. Methods: A multicenter cross-sectional study obtained data from adults presenting to otolaryngology clinics at five sites in Canada, Italy, and Spain. Investigators compared the endoscopically measured depth from sill to nasopharynx along the nasal floor to the facial measurements “curved distance from the alar-facial groove along the face to the tragus” and “distance from the tragus to a plane perpendicular to the philtrum.” When sinus CT images were available, the distance from the nasopharynx to nasal sill was also collected. Results: 371 patients participated in the study (41% women; 51 years old, SD 18). The average endoscopic depth was 9.4 cm (SD 0.86) and 10.1 cm (SD 0.9) for women and men, respectively (p<0.001; 95% CI 0.46 to 0.86). Perpendicular distance was strongly correlated to NP depth (r=0.775; p<0.001), with an average underestimation of 0.1 cm (SD 0.65; 95% CI 0.06 to 0.2). The equation: ND(cm) = perpendicular distance*0.773 + 2.344, generated from 271 randomly selected participants, and validated on 100 participants, resulted in a 0.03 cm prediction error (SD 0.61; 95% CI -0.08 to 0.16). Conclusions: Nasopharyngeal depth can be accurately approximated by the distance from the tragus to a plane perpendicular to philtrum. The generated predictive equation was most accurate but not likely clinically relevant.

In the early 2010s, scientists realized that CRISPR/Cas9, a bacterial immune defense system against viruses that involves the CRISPR-associated protein #9 (Cas9) endonuclease enzyme, single-guide RNAs (sgRNAs), and PAM recognition, could be used to intentionally manipulate genes, essentially changing gene expression and regulation in such a way that would allow for a customized genome. Since then, CRISPR technology has revolutionized medical research and the biotechnology industry, and its newfound capabilities have scientists asking if CRISPR can be used to modify genes in such a way that would cure or treat certain harmful or life-threatening diseases. There have been CRISPR-based clinical studies done to treat β-thalassemia (TDT), sickle-cell disease (SCD), the human immunodeficiency virus (HIV), and several other genetic and non-hereditary diseases, but there is still a long way to go before CRISPR can become a widespread treatment for many more such diseases (Ebina et al., 2013; Esrick et al., 2021; Frangoul et al., 2021). Currently, researchers are looking to see if CRISPR is an accurate, specific, non-harmful, and effective treatment for these diseases, which means addressing and eliminating potential concerns about its safety and efficacy through extensive pre-clinical and clinical research, as well as overcoming moral and social obstacles. In this review, I will look at how the CRISPR/Cas9 gene-editing system can be applied in humans to prevent, cure, or treat these diseases, as well as what needs to be done before the CRISPR/Cas9 system can be made publicly available as a medical treatment for diseases.

• Non-functional larynx (NFL) was found to affect 30.9 % of patients with locally advanced laryngeal cancer who underwent curative non-surgical laryngeal preservation treatment for stage III/IV disease • The key measures of NFL were long-term gastrostomy and tracheostomy dependence, functional laryngectomy and chronic aspiration. • Multivariate analyses identified current smoking to be associated with 6.8-fold increase in NFL • Patients with pre-treatment hemi-laryngeal fixation were 3.4 times more likely to experience locoregional recurrence.

Ecological knowledge is produced through hypothetico-deductive methods fueled by natural history observations. Nevertheless, the biologist-naturalist is becoming a rare species. The lack of incentive and financial investment to natural history related courses, as taxonomy, field biology, and organismal biology is constantly diminishing the graduation of ecologists with first-hand knowledge about nature. The interdependence between natural history and ecology science demands more student training in natural history while updating college curricula and teaching strategies to increase the number of graduates with significant field experiences.

The Ponto-Caspian Bloody-red mysid shrimp (Hemimysis anomala) was discovered in a large freshwater reservoir in the south-east of England in 2020 (Abberton reservoir, Essex, UK). The shrimp was discovered while carrying out aquatic invertebrate surveys across a range of permanent, semi-permanent and seasonal habitats between October and December 2020. The shrimp were found in semi-permanent lagoons adjacent to and connected to the main reservoir and in shallow water bays in the main reservoir. Surveys conducted in January 2021 along a reservoir wall also found the shrimp but no accurate abundance estimates were made. Surveys conducted across the same sites with increased effort in July 2021 did not find any individuals in lagoons, bays or off the reservoir wall in either shallow or deep shelves. The identity of the species was confirmed with high magnification inverted light microscopy due to the shape and setae distribution of the antennal scale and telson in addition to the characteristic bloody red colour of the shrimp pre-preservation. Previous introductions of this species to the UK have been identified before, but whether these propagules arrived from natural or anthropogenic introductions was not clear. Abberton reservoir has no public access for boating or recreational activities other than a small, restricted local angling group but is an internationally important site for migratory and overwintering waterfowl and waders. The migration routes of several waterfowl species for which Abberton is noted would mean that this new shrimp species is likely to have been introduced from either its native range or from its expanded non-native range in the UK or Netherlands by birds. It is not yet confirmed that this discovery represents a successful invasion of this species at Abberton and if it is, when it arrived or what effects it may be having on the food web of this site.

We report here a case of IMOS of the tibia shafts, diagnosed in a 53-year-old man. Medical history did not reveal a history of trauma or infection or familial bone disease and all other causes of osteosclerosis were excluded. The X-Rays showed extensive sclerotic intramedullary lesion of the tibia shafts

Severe Acute Respiratory Coronavirus Syndrome 2 (SARS-CoV-2) is a new human coronavirus family discovered during the highly communicable respiratory disease outbreak in Wuhan, China, in 2019. Various COVID-19 vaccines are up to 95% effective against symptomatic infections caused by the COVID-19. Whether people with PD or PS have an increased risk of COVID-19 and are associated with a higher risk of death is still uncertain. In this study, we report eleven cases of PD patients who died whitin 24 hours after vaccination with the Sinopharm. All patients were over 79 years old (84.64 ± 5.08). All patients were SARS-CoV2 PCR negative and took their first dose of the Sinopharm. All patients had a duration of more than 5 years with PD. All patients presented to the hospital less than 12 hours after vaccination. All patients died less than 24 hours after vaccination. In this study, All the patients were elderly and hypertension and diabetes were seen in 11 (100%) and 7 (63.6%) patients which could reinforce the hypothesis that older patients with PD should be vaccinated more cautiously and these patients should be discussed the vaccine with their physician especially in patients who have other comorbidities. Because our report was a case series study, we only identified patients, and the causality could not be assumed or proven.

How populations diverge into different lineages is a central issue in evolutionary biology. Despite the increasing evidence indicating that such divergences do not need geographic isolation, numerous phenotypic differentiations show a distributional correspondence. In addition, gene flow has been widely detected during and through such diverging processes. We used one widely distributed Aquilegia viridiflora complex as a model system to examine genomic differentiation and corresponding phenotypic variations along geographic gradients. Our phenotypic analyses of 90 individuals from 20 populations from northwest to northeast China identified two phenotypic groups along the geographic cline. All examined traits are distinct between them although a few intermediate individuals occur in their contacting regions. We further sequenced the genomes of the representative individuals of each population. However, we recovered four distinct genetic lineages based on both nuclear genomes and plastomes that were different from phenotypic differentiation. In particular, we recovered numerous genetic hybrids in the contact regions of four lineages. Gene flow is widespread and continuous between four lineages but much higher between contacting lineages than geographically isolated lineages. In addition, many genes with fast lineage-specific mutations were identified to be involved in local adaptation. Our results suggest that both geographic isolation and local selection exerted by the environment may together create geographic distributions of phenotypic variations as well as the underlying genomic divergences in numerous lineages.