Forget me not: The effect of doxycycline on human declarative memory.

Investigations into neuroprotective drugs are in high demand for the treatment of neurodegenerative diseases, such as multiple sclerosis or Alzheimer's disease, but also psychiatric disorders, such as depression, trauma, and substance use. One potential drug class being investigated are tetracyclines impacting on a variety of neuroprotective mechanisms. At the same time, tetracyclines like doxycycline have been suggested to affect human fear and spatial memory as well as reducing declarative memory retention. Based on the assumed necessity for synaptic consolidation in hippocampus-dependent learning, we hypothesised declarative memory may be similarly impaired by doxycycline as fear and spatial memory. Therefore, in this study we investigate the potential diminishing effects of doxycycline on consolidation of declarative memory in healthy humans. Additionally, to test for effect specificity we assessed motor memory, sustained attention, and processing speed. We administered a neuropsychological test battery in three independent randomized placebo-controlled double-blind trials (RCTs), in which healthy young volunteers (total N = 252) either received a single oral dose doxycycline (200 mg, n = 126) or placebo (n = 126) in a between-subject design. We found no evidence for a detrimental effect of doxycycline on declarative memory; instead, doxycycline improved declarative learning (p-value=0.022, Cohen's d=0.15) and memory consolidation (p=0.040, d=0.26). Contrarily, doxycycline slightly reduced motor learning (p=0.001, d=0.10) but subtly strengthened long-term motor memory (p=0.001, d=0.10). These results suggest that doxycycline can improve declarative learning and memory without having long term negative effects on other cognitive domains in healthy humans. Our results give hope to further investigate doxycycline in neuroprotective treatment applications.

Medical treatment of miscarriage using misoprostol-a retrospective study.

PURPOSE: The treatment of early miscarriage with medication is effective and low in side effects. Nevertheless, no uniform dosage regimen has yet been established, nor has it been possible to determine whether previous pregnancies and births with their respective modes of delivery play a role in the effectiveness of Misoprostol. This study aimed to find predictive parameters for successful treatment with Misoprostol in early miscarriage. METHODS: In a retrospective study at the Otto von Guericke University Women's Hospital, records of patients with early miscarriage and medical treatment using Misoprostol from 2018 to 2021 were reviewed for this purpose. The need for a curettage subsequent to treatment was scored as a parameter of failure. The data were analyzed using Statistical Package for the Social Science Version 28.0. The significance level was set to 0.050. RESULTS: We found that successful therapy with misoprostol was seen in 86% (n = 114). 14% (n = 20) of the patients had curettage after taking Misoprostol as advised. Out of 134 women, 16% (n = 21) reported mild side effects, with nausea as the leading one (9.2% (n = 12)). Significance was found comparing the measurement of double endometrial stripe thickness after the second cycle of Misoprostol in women with and without curettage after medical treatment (exact value two-sided 0.035 at p < 0.05). A cutoff value at 8.8 mm was calculated using ROC Analysis. CONCLUSIONS: Our results indicate that the treatment of early miscarriage in the first trimester with Misoprostol is effective and has few side effects. The measurement of the endometrial stripe thickness after the second cycle of Misoprostol via transvaginal ultrasound could present a predictive marker during therapy.

Pharmacological memory modulation to augment trauma-focused psychotherapy for PTSD: a systematic review of randomised controlled trials.

Trauma-focused psychotherapy (tf-PT) is the first-line treatment for posttraumatic stress disorder (PTSD). Tf-PT focuses on processing and modulating trauma memories. Not all patients benefit, however, and there is room for improvement of efficacy. Pharmacologically augmenting trauma memory modulation in the context of tf-PT may help optimise treatment outcome. To systematically review effects of pharmacologically augmented memory modulation in the context of tf-PT for PTSD (PROSPERO preregistration ID: CRD42021230623). We conducted a systematic review of randomised controlled trials of psychotherapy treatment for PTSD. We included placebo-controlled studies that augmented at least one treatment session pharmacologically targeting memory extinction or reconsolidation. We calculated post-treatment between group (pharmacological augmentation vs placebo control) effect sizes of PTSD symptom severity. We included 13 RCTs. There was large heterogeneity in augmentation procedure and methodological quality. Four studies showed significantly greater PTSD symptom reduction in the pharmacological augmentation group (propranolol, hydrocortisone, dexamethasone, D-cycloserine) compared to placebo. Seven studies showed no significant effect of pharmacological augmentation compared to placebo (D-cycloserine, rapamycin, mifepristone, propranolol, mifepristone combined with D-cycloserine, methylene blue). Two studies showed significantly smaller PTSD symptom reduction in the pharmacological augmentation group (D-cycloserine, dexamethasone) compared to placebo. Results of pharmacological augmentation were mixed overall and heterogenous for the pharmacological agents tested in more than one study. Additional studies and replications are needed to identify which pharmacological agents work, in which combination and to identify patient groups that benefit most to tailor PTSD treatment.

Circadian influence on intrusive re-experiencing in trauma survivors' daily lives.

Background: The core clinical feature of posttraumatic stress disorder (PTSD) is recurrent re-experiencing in form of intrusive memories. While a great number of biological processes are regulated by sleep and internal biological clocks, the effect of 24-hour biological cycles, named circadian rhythm, has not been investigated in the context of intrusive memories. Objective: Here we examined effects of time of day on frequency and characteristics of intrusive re-experiencing. Methods: Fifty trauma survivors reported intrusive memories for 7 consecutive days using ecological momentary assessment in their daily life. We investigated (i) time-of-day dependent effects on frequency and distribution of intrusive re-experiencing in the overall sample as well as in PTSD versus non-PTSD and (ii) time-of-day dependent effects on the memory characteristics intrusiveness, vividness, nowness and fear. Results: Intrusive memories showed a curvilinear pattern that peaked at 2pm. Intrusive memories in the PTSD group showed a constant level of intrusive re-experiencing in the afternoon and evening, whereas a descending slope was present in the non-PTSD group. In PTSD, intrusive memories might thus be experienced in a more time-scattered fashion throughout the day, indicating chronodisruption. Intrusion characteristics did not follow this pattern. Conclusion: Although preliminary and based on a small sample size, these findings contribute to a better understanding of the everyday occurrence and characteristics of intrusive memories, and point to the added value of examining time-dependent effects, which can directly inform prevention and intervention science.

Antecedentes: La característica clínica central del trastorno de estrés postraumático (TEPT) es la re-experimentación recurrente en forma de recuerdos intrusivos. Si bien un gran número de procesos biológicos están regulados por el sueño y los relojes biológicos internos, el efecto de los ciclos biológicos de 24 horas, llamado ritmo circadiano, no ha sido investigado en el contexto de los recuerdos intrusivos.Objetivo: Aquí examinamos los efectos de la hora del día sobre la frecuencia y características de la re-experimentación intrusiva.Métodos: Cincuenta sobrevivientes de trauma reportaron recuerdos intrusivos por 7 días consecutivos usando la evaluación ecológica momentánea en su vida diaria. Investigamos (i) los efectos dependientes de la hora del día sobre la frecuencia y distribución de los recuerdos intrusivos en la muestra general, así como en TEPT versus no TEPT y (ii) los efectos dependientes de la hora del día sobre las características de la intrusividad de los recuerdos, vividez, momento presente y miedo.Resultados: Los recuerdos intrusivos mostraron un patrón curvilíneo que alcanzaba su punto máximo a las 2 pm. Los recuerdos intrusivos en el grupo con TEPT mostraron un nivel constante de re-experimentación intrusiva en la tarde y la noche, mientras que en el grupo sin TEPT se observó una pendiente descendiente. En el TEPT, los recuerdos intrusivos pueden experimentarse en una manera más dispersa en el tiempo a lo largo del día, lo que indica cronodisrupción. Las características de intrusión no siguieron este patrón.Conclusión: Aunque son preliminares y se basan en un tamaño de muestra pequeño, estos hallazgos contribuyen a una mayor comprensión de la ocurrencia cotidiana y las características de los recuerdos intrusivos y apuntan al valor agregado de examinar sus efectos dependientes del tiempo, que pueden informar directamente a la ciencia de la prevención e intervención.

Controversial Trials First: Identifying Disagreement Between Clinical Guidelines and New Evidence.

Clinical guidelines integrate latest evidence to support clinical decision-making. As new research findings are published at an increasing rate, it would be helpful to detect when such results disagree with current guideline recommendations. In this work, we describe a software system for the automatic identification of disagreement between clinical guidelines and published research. A critical feature of the system is the extraction and cross-lingual normalization of information through natural language processing. The initial version focuses on the detection of cancer treatments in clinical trial reports that are not addressed in oncology guidelines. We evaluate the relevance of trials retrieved by our system retrospectively by comparison with historic guideline updates and also prospectively through manual evaluation by guideline experts. The system improves precision over state-of-the-art literature research strategies while maintaining near-total recall. Detailed error analysis highlights challenges for fine-grained clinical information extraction, in particular when extracting population definitions for tumor-agnostic therapies.

Distinct Clinicopathological and Prognostic Features of Thin Nodular Primary Melanomas: An International Study from 17 Centers.

BACKGROUND: Nodular melanoma (NM) is more likely to be fatal compared with other melanoma subtypes, an effect attributed to its greater Breslow thickness. METHODS: Clinicopathological features of NM and superficial spreading melanoma (SSM) diagnosed in 17 centers in Europe (n = 15), the United States, and Australia between 2006 and 2015, were analyzed by multivariable logistic regression analysis, with emphasis on thin (T1 ≤ 1.0 mm) melanomas. Cox analysis assessed melanoma-specific survival. All statistical tests were two sided. RESULTS: In all, 20 132 melanomas (NM: 5062, SSM: 15 070) were included. Compared with T1 SSM, T1 NM was less likely to have regression (odds ratio [OR] = 0.46, 95% confidence interval [CI] = 0.29 to 0.72) or nevus remnants histologically (OR = 0.60, 95% CI = 0.42 to 0.85), and more likely to have mitoses (OR = 1.97, 95% CI = 1.33 to 2.93) and regional metastasis (OR = 1.77, 95% CI = 1.02 to 3.05). T1 NM had a higher mitotic rate than T1 SSM (adjusted geometric mean = 2.2, 95% CI = 1.9 to 2.5 vs 1.6, 95% CI = 1.5 to 1.7 per mm2, P < .001). Cox multivariable analysis showed a higher risk for melanoma-specific death for NM compared with SSM for T1 (HR = 2.10, 95% CI = 1.24 to 3.56) and T2 melanomas (HR = 1.30, 95% CI = 1.01 to 1.68), and after accounting for center heterogeneity, the difference was statistically significant only for T1 (HR = 2.20, 95% CI = 1.28 to 3.78). The NM subtype did not confer increased risk within each stratum (among localized tumors or cases with regional metastasis). CONCLUSIONS: T1 NM (compared with T1 SSM) was associated with a constellation of aggressive characteristics that may confer a worse prognosis. Our results indicate NM is a high-risk melanoma subtype that should be considered for inclusion in future prognostic classifications of melanoma.

[Examination procedure and description of skin lesions]. / Untersuchungsgang und Effloreszenzenlehre.

The dermatologic examination follows a clear structure. After a short history is taken, the whole skin is inspected. The description, which is ideally provided in writing, forces one to look at the skin more closely. The description should include an accurate description of the location, the distribution, the form, and the type of lesion. The article contains tables with internationally approved definitions to describe skin changes. The analysis of these findings allows one to deduce pathophysiologic mechanisms occurring in the skin and to deduce hypotheses, i. e., suspected and differential diagnoses. These are confirmed or excluded by further diagnostic measures. The expert comes to a diagnosis very quickly by a pattern-recognition process, whereby novices must still develop this kind of thinking. Experts can minimize cognitive bias by reflective analytical reasoning and reorganization of knowledge.

Head Lice.

BACKGROUND: Conflicting information about the proper treatment of head lice has given rise to uncertainty among patients and treating personnel. For example, the reported efficacy of permethrin fell from 97% in the 1990s to 30% in 2010. METHODS: Review of the literature based on a selective search of PubMed. RESULTS: In Germany, outbreaks of head lice mainly occur among 5- to 13-year-olds returning to school after the summer vacation. Nymphs hatch from eggs after an average of 8 days and become sexually mature lice over the ensuing 9 days. The main route of transmission is direct head-to-head contact; transmission via inanimate objects is of no relevance. Symptoms arise 4-6 weeks after an initial infestation; many affected persons have no symptoms at all. Wet combing is the most sensitive method of establishing the diagnosis and monitoring treatment. Resistance to neurotoxic pediculocidal drugs is increasing around the world. Dimethicones are the treatment of choice, with 97% efficacy. Outbreaks must be managed with the synchronous treatment of all infested persons to break the chain of infestation. If the agent used is not ovicidal, the treatment must be repeated in 8-10 days and sometimes in a further 7 days as well. CONCLUSION: Outbreaks of head lice can be successfully terminated by synchronous treatment with ovicidal dimethicones.