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External ear melanoma (EEM) belongs to extremely rare melanoma locations. So far, only single cases of EEM have been described in terms of dermoscopic presentations. This case study report presents dermoscopic patterns of EEM in six patients. The retrospective case study was based on medical documentation (epidemiological, anamnestic, clinical, videodermoscopic, and histopathologic) of consecutive patients who were diagnosed with melanoma located on the external ear between January 2013 and May 2021 in three diagnostic dermatologic centers. In four of six cases, the melanoma was placed on the helix. The histopathological diagnoses included 1/6 lentigo maligna and 5/6 invasive melanomas. The dermoscopic pattern of facial melanoma (FM) was present in 3/6 cases, 1/6 exhibited the typical superficial spreading pattern (one with nodular invasion), 1/6 the multicomponent asymmetric pattern, and 1/6 the hypomelanotic type. Five melanomas presented numerous (3–6) dermoscopic structures characteristic for each dermoscopic subtype. In conclusion, dermoscopy has proved effective for detection of both difficult and easy-to-diagnose EEM, but also in differentiating their dermoscopic subtypes.

Background Patients attending GUM clinics may disclose sexual violence. Are GUM/HIV trainees equipped to manage these cases? Aim To assess the experience and training needs of GUM/HIV trainees in managing patients disclosing sexual violence (SV patients). Method An e-survey was open to GUM/HIV trainees for 12 weeks from February 2011. Data were analysed in Excel. Results Of the 158 current GUM/HIV trainees, 44 (28%) completed surveys. All respondents managed SV patients and 59% managed ≥ 1 SV case/month. Of these, 98% had seen females, 66% males, 73% 16–17 years/olds, 34% 13–15 years/olds, 5% under-13s. All respondents routinely asking about SV saw ≥ 1 case/month vs 50% of those who rarely/never asked. Confidence increased with frequency of seeing patients: 96% (25/26) seeing ≥ 1 SV patient/month felt confident vs 67% (12/18) seeing <1/month. Confidence in managing female, male and under-18 SV patients was reported in 86%, 79% and 58% respectively. In the six units with a dedicated SV clinic two trainees had worked in one, overall, 92% would have liked to. Similarly, 14% had worked in a Sexual Assault Referral Centre, 81% would have liked to. Respondents had trained in safeguarding children, adult SV, chain of evidence, vulnerable adults and domestic violence in 92%, 82%, 76%, 64%, 32% respectively. Abstract P165 Table 1 details respondents' reported competencies and training availability in 2010 curriculum skills. Abstract P165 Table 1 Competent (%) Not competent, training available (%) Not competent, training not available (%) Emergency contraception counselling 100 0 0 Referring to support organisations 90 10 0 Prescribing STI/HIV/Hep B prophylaxis 90 10 0 SV history taking and risk assessment in u-18s 89 4 7 Forensic exam counselling/documenting injuries 64 29 7 Documenting history/exam for medico-legal report 46 19 35 Conclusions Wide variation exists in reported SV experience, training received and training availability, in the 28% of trainees responding. Regular accessible training is needed in identifying and managing patients disclosing SV.

Comparative studies were performed to determine the activity and cytotoxicity of amphotericin B (AmB) and its derivatives on standard strain of Saccharomyces cerevisiae and its transformants with cloned genes from Candida albicans encoding multidrug resistance (MDR) pumps of ATP-binding cassette and major facilitator superfamilies. The AmB derivatives: amphotericin B 3-dimethylaminopropyl amide and N -methyl- N - D -fructopyranosylamphotericin B methyl ester were shown to be fungistatic and fungicidal towards MDR strains, by membrane permeabilization mechanism. Antibiotic-cell interaction monitored by energy transfer method indicates similar membrane affinity in parent strain and its MDR transformants. Experiments with fungal cells loaded with rhodamine 6G point to lack of competition between this dye and AmB and its derivatives for efflux driven by CDR2p. It can be thus assumed that AmB and its derivatives overcome fungal MDR by not being substrates of the multidrug exporting pumps, presumably due to their large molecular volumes.

* Precipitating factors are events or experiences associated with the initial appearance of sexual dysfunction, for instance, childbirth, relationship problems such as infidelity, sexual dysfunction in a partner, physical illness or surgery (for example, hysterectomy or mastectomy), medication (for instance, antidepressants), depression or anxiety and sexual assault. Regrettably, iatrogenic sexual dysfunction in women is not uncommon, precipitated by medical procedures such as episiotomy, Wertheim's hysterectomy, oophorectomy, repair of a vaginal prolapse and mastectomy or colposcopy.1 It is noteworthy, however, that contrary to common belief, simple hysterectomy often leads to improved sexual function. Dyspareunia (pain during sexual intercourse) is a symptom rather than a disorder per se but warrants a mention in the present context. Dyspareunia may be superficial or deep with physical cause(s) and, often, secondary psychological reactions, such as avoidance of sexual activity, impairment of sexual desire and relationship difficulties. Superficial dyspareunia may arise from a lack of sexual arousal and adequate lubrication, vaginal infection (thrush or Bartholin's cyst), vulval dermatoses or vulvodynia. Deep dyspareunia can occur in association with pelvic infection, ovarian pathology or endometriosis. Episiotomy scars with granulation tissue, and perineal tears during childbirth may be troublesome causes of dyspareunia.

Neuropharmacological and human clinical studies have suggested that the brain dopaminergic system is substantively involved in normal and pathological phenotypes of attention. Dopamine transporter gene ( SLC6A3 ) was proposed as a candidate gene for Attention-Deficit/Hyperactivity Disorder (ADHD). We investigated the effect of the SLC6A3 variants on cognitive performance in ADHD and healthy children and teenagers. Participants completed cognitive tasks measuring attentional switching, selective and sustained attention, and effectiveness of alerting, orienting and executive attention. We estimated the effects of 40 bp variable number of tandem repeat (VNTR) polymorphism located in the 3′ untranslated region (3′ UTR) (9-repeat vs 10-repeat allele) of the SLC6A3 gene, ADHD diagnosis, age, and their interactions as predictors of cognitive performance. ADHD children demonstrated deficits in most of the examined attention processes, persistent within the examined age range (9–16 years). No significant effects were observed for the interaction of ADHD and the SLC6A3 polymorphism, but the results revealed a significant main effect of SLC6A3 genotype in the entire research sample. Subjects carrying 9R allele performed the switching task significantly worse in comparison to children with 10R/10R or 10R/11R genotype. SLC6A3 polymorphism moderated age-related improvements in orienting and attentional switching. Results suggest that SLC6A3 genotype influence these attentional/cognitive functions which deficits are not the key symptoms in ADHD.

Aging-related neurological deficits negatively impact mental health, productivity, and social interactions leading to a pronounced socioeconomic burden. Since declining brain dopamine signaling during aging is associated with the onset of neurological impairments, we produced a selective dopamine transporter (DAT) inhibitor to restore endogenous dopamine levels and improve cognitive function. We describe the synthesis and pharmacological profile of (S,S)-CE-158, a highly specific DAT inhibitor, which increases dopamine levels in brain regions associated with cognition. We find both a potentiation of neurotransmission and coincident restoration of dendritic spines in the dorsal hippocampus, indicative of reinstatement of dopamine-induced synaptic plasticity in aging rodents. Treatment with (S,S)-CE-158 significantly improved behavioral flexibility in scopolamine-compromised animals and increased the number of spontaneously active prefrontal cortical neurons, both in young and aging rodents. In addition, (S,S)-CE-158 restored learning and memory recall in aging rats comparable to their young performance in a hippocampus-dependent hole board test. In sum, we present a well-tolerated, highly selective DAT inhibitor that normalizes the age-related decline in cognitive function at a synaptic level through increased dopamine signaling.

In metastatic cancer, the degree of heterogeneity of the tumor microenvironment (TME) and its molecular underpinnings remain largely unstudied. To characterize the tumor–immune interface at baseline and during neoadjuvant chemotherapy (NACT) in high-grade serous ovarian cancer (HGSOC), we performed immunogenomic analysis of treatment-naive and paired samples from before and after treatment with chemotherapy. In treatment-naive HGSOC, we found that immune-cell-excluded and inflammatory microenvironments coexist within the same individuals and within the same tumor sites, indicating ubiquitous variability in immune cell infiltration. Analysis of TME cell composition, DNA copy number, mutations and gene expression showed that immune cell exclusion was associated with amplification of Myc target genes and increased expression of canonical Wnt signaling in treatment-naive HGSOC. Following NACT, increased natural killer (NK) cell infiltration and oligoclonal expansion of T cells were detected. We demonstrate that the tumor–immune microenvironment of advanced HGSOC is intrinsically heterogeneous and that chemotherapy induces local immune activation, suggesting that chemotherapy can potentiate the immunogenicity of immune-excluded HGSOC tumors. Immunogenomic analyses of advanced high-grade serous ovarian cancer samples before and after neoadjuvant chemotherapy show that the tumor–immune microenvironment is intrinsically heterogeneous and that chemotherapy induces local immune activation.