Rejected

(a) To characterize the frequency of objective cognitive deficits and self-perceived cognitive difficulties and (b) to explore demographic and clinical predictors of cognitive dysfunction and cognitive complaints.

Patients with vulvar lichen sclerosus (VLS) are faced with a decreased quality of life and an increased risk of vulvar malignancy. 5-Aminolevulinic acid-based photodynamic therapy (ALA-PDT) can serve as an alternative for refractory VLS patients. However, high-frequency ultrasound (HFUS) has never been introduced in the ALA-PDT outcome assessment for VLS patients.

There is a lack of report of conscious sedation used as a last resort therapy for alleviating severe symptoms. To achieve this goal, dexmedetomidine appears to be a promising option. We report a case of successful two-month long treatment of intravenous (IV) dexmedetomidine added to hydromorphone for intractable cancer pain, restlessness, severe sleep disorder, anxiety, and craving symptoms in a 40-year-old man with active polysubstance use, receiving escalating doses of opioids for intractable abdominal cancer pain together with benzodiazepines. Under dexmedetomidine infusion at 1.2 μg/kg/hour, his symptoms markedly decreased. He could sleep at night and find respite during the day while continuing walking, eating, and other activities. Long-term conscious sedation with IV dexmedetomidine was well tolerated. We did not observe anxiety or agitation rebound during short periods of discontinuation of the infusion. Neither side effects nor tolerance were observed over time. Further research is needed to investigate the indications for conscious sedation and analgesia with dexmedetomidine in palliative patients with a prognosis that is longer than few weeks or uncertain.

Pain may increase the risk for sarcopenia, but existing literature is only from high-income countries, while the mediators of this association are largely unknown. Thus, we aimed to investigate the association between pain and sarcopenia using nationally representative samples of older adults from six low- and middle-income countries (LMICs), and to identify potential mediators.

Present study aimed compared pharmacokinetic profile of sustained-release CaffXtend® capsules (SR-Caffeine) with immediate-release caffeine capsules (IR-Caffeine), and the effect of SR-caffeine on memory, motivation, concentration, and attention. This open-label, randomized, single-dose, two-treatment, two-sequence, two-period, two-way crossover oral bioavailability study block randomized (1:1) healthy subjects ( = 15) to receive SR-Caffeine (200 mg) and IR-Caffeine (200 mg). Blood samples were collected at 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36 and 48 h in each period. Primary study outcome included comparing relative bioavailability of SR-Caffeine 200 mg and IR-Caffeine 200 mg under fasting conditions, and changes in caffeine research visual analogue scale (Caff-VAS) scores ('relaxed', 'alert', 'jittery', 'tired', 'tense', 'headache', 'overall mood' and 'mentally fatigued') were also evaluated. Fifteen subjects completed the study. Mean t was 4.08 ± 2.13h for SR-Caffeine compared to 0.83 ± 0.39h for IR-Caffeine, ( < 0.0001). Similarly, mean t was 7.07 ± 3.48h for SR-Caffeine compared to 5.78 ± 2.11h for IR-Caffeine ( = 0.04189). However, total exposure was similar for SR-Caffeine and IR-Caffeine (90% CI: 89.89-120.50% to 94.49-123.82% for geometric least square mean of ln-transformed AUC and AUC). In the Caff-VAS evaluation, the SR-Caffeine group showed significantly better scores for 'jitteriness', 'tiredness', 'alertness' and 'overall mood' for 8-12 h than the IR-Caffeine group. No adverse events were reported. Results demonstrated sustained release of caffeine over 24 h from SR-Caffeine as compared to IR-Caffeine, which showed significant improvements in the scores for 'relaxed', 'alertness' and 'overall mood' and significantly lower scores for the parameters-'jittery' and 'tired' for extended period. CTRI/2021/06/034185.

Euphorbium is the resinous secretion of Euphorbia resinifera Berg. According to the record, Euphorbium was first used by Roman doctors to treat the emperor's joint pain. In China, it is applied in folk medicine to treat damp-cold or mucous diseases, such as arthralgia and ascites, etc. This herb is used for rheumatoid arthritis and skin tumors in the folklore of northeastern Brazil. Triterpenes are mainly characteristic constituents of Euphorbium, and possibly possess anti-rheumatoid arthritis.

We investigate a 2,000-year genetic transect through Scandinavia spanning the Iron Age to the present, based on 48 new and 249 published ancient genomes and genotypes from 16,638 modern individuals. We find regional variation in the timing and magnitude of gene flow from three sources: the eastern Baltic, the British-Irish Isles, and southern Europe. British-Irish ancestry was widespread in Scandinavia from the Viking period, whereas eastern Baltic ancestry is more localized to Gotland and central Sweden. In some regions, a drop in current levels of external ancestry suggests that ancient immigrants contributed proportionately less to the modern Scandinavian gene pool than indicated by the ancestry of genomes from the Viking and Medieval periods. Finally, we show that a north-south genetic cline that characterizes modern Scandinavians is mainly due to the differential levels of Uralic ancestry and that this cline existed in the Viking Age and possibly earlier.

Chronic anal fissure is a common benign anorectal disease with a high recurrence rate. Pelvic floor physical therapy has been proven effective in the short-term management in patients with chronic anal fissure and pelvic floor dysfunction (PAF-trial). The aim of this study was to determine the outcomes of the PAF-trial and fissure recurrence in patients who completed the 2 months of pelvic floor physical therapy at 1-year follow-up.

Autoimmune diseases triggered by coronavirus disease 2019 (COVID-19) mRNA vaccination have been emerging. Here, we report the case of a 27-year-old Japanese man with autoimmunity-related neutrophilic dermatosis, occurring as an initial cutaneous manifestation of systemic lupus erythematosus with Sjögren syndrome after the second dose of the Pfizer/BioNTech COVID-19 vaccination. The patient presented with urticarial erythema and partially annular erythema on the trunk and extremities with severe pruritus. Histopathological analysis showed vacuolar degeneration at the dermo-epidermal junction and interstitial neutrophil infiltration. We reviewed eight patients, including the aforementioned patient, with exacerbation or new-onset of SLE after COVID-19 vaccination and found the patient had relatively mild symptoms, itchy annular erythema, and positive anti-SS-A/SS-B antibodies. COVID-19 mRNA vaccination can induce the production of type-I interferon, which plays a crucial role in the pathogenesis of SLE and may cause autoimmunity-related neutrophilic dermatosis in susceptible individuals. In the case that itchy annular erythema develops approximately 2 weeks after the vaccination, the possibility of systemic or cutaneous lupus erythematosus should be considered. For an accurate diagnosis, dermatologists should obtain a recent vaccination history and perform complete antibody profiling and skin biopsy for patients presenting with annular or erythema multiforme-like lesions.