New trends on personalized sunscreens.

BACKGROUND/PURPOSE: Nowadays, there are emerging trends in customized and personalized photoprotection, focusing on the innovative approaches to enhance sun protection efficacy tailored to individual needs. METHODS: We conducted an electronic search of the following databases: MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Skin Group Specialised Skin Register, and TESEO. Specific search terms related to personalized photoprotection and the variables of age, genetic predisposition, skin phototype, photodermatosis, and physiological conditions such as pregnancy, as well as lifestyle habits were used. RESULTS/CONCLUSION: The article highlights the challenges and opportunities in adopting personalized photoprotection strategies, aiming to promote skin health and prevent the harmful effects of UV radiation in the era of precision medicine.

Arachnoid bands in hemifacial spasm: an overlooked etiology? Illustrative case.

BACKGROUND: Primary hemifacial spasm (HFS) is usually caused by arterial compression of the facial nerve at the root exit zone at the brainstem. Rarely, a purely venous compression is seen. However, arachnoid bands strangulating the facial nerve have not been recognized as a cause of hemifacial spasm. OBSERVATIONS: The authors present a case of a 24-year-old female who had experienced HFS for 9 years. Endoscopic inspection of the root exit zone revealed no vascular compression but an arachnoid band strangulating the facial nerve. After cutting the band, the lateral spread response disappeared, and the patient was immediately spasm free after the surgery. Two years later, she was still doing well without any spasms. LESSONS: This is the third patient in the authors' series of 535 patients who had no vascular conflict but rather a strangulation of the nerve by arachnoid bands. All patients have remained spasm free. To the authors' knowledge, no other group has reported arachnoid bands as an etiological factor of HFS so far.

Etiology and Management of Recurrent and Persistent Hemifacial Spasm-A Single-Center Experience.

BACKGROUND AND OBJECTIVES: Despite a 90% success rate, microvascular decompression occasionally fails to resolve hemifacial spasm (HFS), necessitating revision surgery. We investigated recurrent cases to identify underlying causes. METHODS: We evaluated patients at our institution who underwent revision microvascular decompression because of recurrent or persistent HFS, assessing recurrence causes, decompression techniques, complications, and outcomes. Data considered included demographics, preoperative symptoms, disease duration, offending vessel, and magnetic resonance findings. Surgical notes and intraoperative videos were reviewed, and telephone interviews were conducted for recent outcomes. RESULTS: Out of our ongoing series of 493 patients, 43 patients (8.7%) required revision surgery with a patient cohort of 33 females and 10 males. The average symptom duration was 10 years. The median time between primary and revision surgery was 14 months. Thirteen patients (30.2%) underwent initial surgery elsewhere. Adhesions of Teflon pledgets to the facial nerve were the primary cause of nonresolution in 23 patients (53.5%), while in 13 (30.2%), a missed vascular compression was identified. Sixteen patients (37.2%) had sufficient decompression by removing the conflicting pledgets. During 10 revisions (23.3%), additional Teflon pledgets were necessary. After a median follow-up of 67 months after revision surgery, 27 patients (62.8%) reported complete spasm resolution. Six patients (14.0%) had a good outcome with over 90% reduction of their spasms, 3 patients (7.0%) stated a fair outcome (50% improvement), while 7 patients (16.3%) had no improvement. CONCLUSION: According to our results, adhesions of Teflon to the facial nerve may cause HFS recurrence. Therefore, whenever possible, Teflon should be placed without nerve contact between the brainstem and the offending vessel. Using a sling or bridge technique seems to be beneficial because it leaves the facial nerve completely free. Persistent symptoms often result from missed offending vessels in the pontomedullary sulcus indicating the benefit of endoscopic inspection of this area with an endoscope.

Comparative efficacy and safety of multimodality treatment for advanced hepatocellular carcinoma with portal vein tumor thrombus: patient-level network meta-analysis.

Background: Portal vein tumor thrombus (PVTT) is a common complication and an obstacle to treatment, with a high recurrence rate and poor prognosis. There is still no global consensus or standard guidelines on the management of hepatocellular carcinoma (HCC) with PVTT. Increasing evidence suggests that more aggressive treatment modalities, including transarterial chemoembolization, radiotherapy, targeted therapy, and various combination therapies, may improve the prognosis and prolong the survival of advanced hepatocellular carcinoma (aHCC) patients with PVTT. We aim to comprehensively review and compare the efficacy and safety of these advanced options for aHCC with PVTT. Methods: A comprehensive literature search was conducted on PubMed and EMBASE for phase II or III randomized controlled trials (RCTs) investigating multimodality treatments for aHCC with PVTT. Kaplan-Meier curves for overall survival (OS) and progression-free survival were constructed to retrieve individual patient-level data to strengthen the comparison of the benefits of all multimodality treatments of interest. Each study was pooled in a fixed-effects network meta-analysis (NMA). We also conducted subgroup analyses using risk ratios extracted from each study, including viral etiology, Barcelona Clinic Liver Cancer (BCLC) staging, alpha-fetoprotein (AFP) levels, macrovascular invasion or portal vein tumor thrombosis, and extrahepatic spread. Multimodality treatments were ranked using SUCRA scores. Results: We identified 15 randomized controlled trials with 16 multimodality regimens that met the inclusion criteria. Among them, 5,236 patients with OS results and 5,160 patients with PFS results were included in the analysis. The hepatic arterial infusion chemotherapy of fluorouracil, leucovorin, and oxaliplatin (HAIC-FO) showed OS and PFS benefits over all the other therapies. In terms of OS, HAIC-FO, nivolumab, and TACE+Len were superior to sorafenib, lenvatinib, and donatinib monotherapies, as well as HAIC-FO+Sor. In terms of PFS, TACE+Len showed better benefits than lenvatinib, donatinib, and tremelimumab+durvalumab. A low heterogeneity (I 2 < 50%) and consistency were observed. The SUCRA score for OS ranked HAIC-FO+sorafenib as the best treatment option among all multimodality treatments in hepatitis B, MVI, or PVTT with EHS and AFP 400 µg/L subgroups. Conclusion: HAIC-FO and HAIC-FO+sorafenib are statistically better options for unresectable hepatocellular carcinoma with PVTT among the multimodality treatments, and their effective and safe implementation may provide the best outcomes for HCC-PVTT patients.

The influence of cortical activity on perception depends on behavioral state and sensory context.

The mechanistic link between neural circuit activity and behavior remains unclear. While manipulating cortical activity can bias certain behaviors and elicit artificial percepts, some tasks can still be solved when cortex is silenced or removed. Here, mice were trained to perform a visual detection task during which we selectively targeted groups of visually responsive and co-tuned neurons in L2/3 of primary visual cortex (V1) for two-photon photostimulation. The influence of photostimulation was conditional on two key factors: the behavioral state of the animal and the contrast of the visual stimulus. The detection of low-contrast stimuli was enhanced by photostimulation, while the detection of high-contrast stimuli was suppressed, but crucially, only when mice were highly engaged in the task. When mice were less engaged, our manipulations of cortical activity had no effect on behavior. The behavioral changes were linked to specific changes in neuronal activity. The responses of non-photostimulated neurons in the local network were also conditional on two factors: their functional similarity to the photostimulated neurons and the contrast of the visual stimulus. Functionally similar neurons were increasingly suppressed by photostimulation with increasing visual stimulus contrast, correlating with the change in behavior. Our results show that the influence of cortical activity on perception is not fixed, but dynamically and contextually modulated by behavioral state, ongoing activity and the routing of information through specific circuits.

The feasibility and acceptability of an app-based intervention with brief behavioural support (APPROACH) to promote brisk walking in people diagnosed with breast, prostate and colorectal cancer in the UK.

INTRODUCTION: Increased moderate to vigorous physical activity (MVPA) can improve clinical and psychosocial outcomes for people living with and beyond cancer (LWBC). This study aimed to assess the feasibility and acceptability of trial procedures in a pilot randomised controlled trial (RCT) of a theory-driven app-based intervention with behavioural support focused on promoting brisk walking (a form of MVPA) in people LWBC (APPROACH). METHODS: Participants diagnosed with breast, prostate or colorectal cancer were recruited from a single UK hospital site. Assessments at baseline and 3 months included online questionnaires, device-measured brisk walking (activPAL accelerometer) and self-reported weight and height. Participants were randomised to intervention or control (care as usual). The intervention comprised a non-cancer-specific app to promote brisk walking (National Health Service 'Active 10') augmented with print information about habit formation, a walking planner and two behavioural support telephone calls. Feasibility and acceptability of trial procedures were explored. Initial estimates for physical activity informed a power calculation for a phase III RCT. A preliminary health economics analysis was conducted. RESULTS: Of those medically eligible, 369/577 (64%) were willing to answer further eligibility questions and 90/148 (61%) of those eligible were enrolled. Feasibility outcomes, including retention (97%), assessment completion rates (>86%) and app download rates in the intervention group (96%), suggest that the trial procedures are acceptable and that the intervention is feasible. The phase III RCT will require 472 participants to be randomised. As expected, the preliminary health economic analyses indicate a high level of uncertainty around the cost-effectiveness of the intervention. CONCLUSIONS: This pilot study demonstrates that a large trial of the brisk walking intervention with behavioural support is both feasible and acceptable to people LWBC. The results support progression onto a confirmatory phase III trial to determine the efficacy and cost-effectiveness of the intervention.

Neuronal Ensembles in the Amygdala Allow Social Information to Motivate Later Decisions.

Social experiences carry tremendous weight in our decision-making, even when social partners are not present. To determine mechanisms, we trained female mice to respond for two food reinforcers. Then, one food was paired with a novel conspecific. Mice later favored the conspecific-associated food, even in the absence of the conspecific. Chemogenetically silencing projections from the prelimbic subregion (PL) of the medial prefrontal cortex to the basolateral amygdala (BLA) obstructed this preference while leaving social discrimination intact, indicating that these projections are necessary for socially driven choice. Further, mice that performed the task had greater densities of dendritic spines on excitatory BLA neurons relative to mice that did not. We next induced chemogenetic receptors in cells active during social interactions-when mice were encoding information that impacted later behavior. BLA neurons stimulated by social experience were necessary for mice to later favor rewards associated with social conspecifics but not make other choices. This profile contrasted with that of PL neurons stimulated by social experience, which were necessary for choice behavior in social and nonsocial contexts alike. The PL may convey a generalized signal allowing mice to favor particular rewards, while units in the BLA process more specialized information, together supporting choice motivated by social information.

Thio-2 inhibits key signaling pathways required for the development and progression of castration resistant prostate cancer.

Therapies that abrogate persistent androgen receptor (AR) signaling in castration resistant prostate cancer (CRPC) remain an unmet clinical need. The N-terminal domain (NTD) of the AR that drives transcriptional activity in CRPC remains a challenging therapeutic target. Herein we demonstrate that BAG-1 mRNA is highly expressed and associates with signaling pathways, including AR signaling, that are implicated in the development and progression of CRPC. In addition, interrogation of geometric and physiochemical properties of the BAG domain of BAG-1 isoforms identifies it to be a tractable but challenging drug target. Furthermore, through BAG-1 isoform mouse knockout studies we confirm that BAG-1 isoforms regulate hormone physiology and that therapies targeting the BAG domain will be associated with limited 'on-target' toxicity. Importantly, the postulated inhibitor of BAG-1 isoforms, Thio-2, suppressed AR signaling and other important pathways implicated in the development and progression of CRPC to reduce the growth of treatment resistant prostate cancer cell lines and patient derived models. However, the mechanism by which Thio-2 elicits the observed phenotype needs further elucidation since the genomic abrogation of BAG-1 isoforms was unable to recapitulate the Thio-2 mediated phenotype. Overall, these data support the interrogation of related compounds with improved drug-like properties as a novel therapeutic approach in CRPC, and further highlight the clinical potential of treatments that block persistent AR signaling which are currently undergoing clinical evaluation in CRPC.

Endoscope-Assisted Microsurgery for Posterior Fossa Skull Base Meningioma Surgery: Technique and Results.

BACKGROUND AND OBJECTIVES: Surgery of posterior fossa meningiomas is extremely challenging even for experienced skull base surgeons because of the close proximity to cranial nerves and tight spaces. Endoscope-assisted surgery for posterior fossa meningiomas can enable a high degree of tumor resection even when using small approaches. This study describes the advantage of endoscope-assisted microneurosurgery in resection of posterior fossa skull base meningiomas and the clinical outcome. METHODS: All endoscope-assisted surgeries for resection of posterior fossa meningiomas performed between 2002 and 2016 in our department were retrospectively analyzed. For data acquisition, the patient files were used. Tumor size and extent of resection were evaluated on pre- and postoperative magnetic resonance imaging. The value of endoscope assistance was assessed according to the intraoperative videos and the surgical notes. Complications and long-term outcomes were evaluated. RESULTS: We identified 39 female and 10 male patients. The mean age of the patients at the time of surgery was 55 years, ranging from 25 to 78 years. The mean follow-up was 93.8 months. A total of 41% of the tumors were large to giant. The retrosigmoid approach was used in most patients (45). A gross total resection could be achieved in 38 patients (78%). In 11 patients (22%), a near total resection was performed. In 27 patients (55%), a hidden residual tumor, which could not been visualized with the operating microscope, was identified with the endoscope. In 6 patients (22.2%), the internal auditory canal was visualized, in 9 patients (33.3%), the Meckel's cave was visualized, and in 5 patients (18.5%), both were visualized under endoscope assistance. In 26 of those patients (96.3%), the residual tumor was resected under endoscopic view. CONCLUSION: Endoscope-assisted surgery for posterior fossa skull base meningiomas enables a high degree of tumor resection, avoids more invasive skull base approaches, and reduces the amount of cerebellar retraction.

The single-cell transcriptome program of nodule development cellular lineages in Medicago truncatula.

Legumes establish a symbiotic relationship with nitrogen-fixing rhizobia by developing nodules. Nodules are modified lateral roots that undergo changes in their cellular development in response to bacteria, but the transcriptional reprogramming that occurs in these root cells remains largely uncharacterized. Here, we describe the cell-type-specific transcriptome response of Medicago truncatula roots to rhizobia during early nodule development in the wild-type genotype Jemalong A17, complemented with a hypernodulating mutant (sunn-4) to expand the cell population responding to infection and subsequent biological inferences. The analysis identifies epidermal root hair and stele sub-cell types associated with a symbiotic response to infection and regulation of nodule proliferation. Trajectory inference shows cortex-derived cell lineages differentiating to form the nodule primordia and, posteriorly, its meristem, while modulating the regulation of phytohormone-related genes. Gene regulatory analysis of the cell transcriptomes identifies new regulators of nodulation, including STYLISH 4, for which the function is validated.

Hydrogen/Deuterium Exchange Mass Spectrometry Provides Insights into the Role of Drosophila Testis-Specific Myosin VI Light Chain AndroCaM.

In Drosophila testis, myosin VI plays a special role, distinct from its motor function, by anchoring components to the unusual actin-based structures (cones) that are required for spermatid individualization. For this, the two calmodulin (CaM) light-chain molecules of myosin VI are replaced by androcam (ACaM), a related protein with 67% identity to CaM. Although ACaM has a similar bi-lobed structure to CaM, with two EF hand-type Ca2+ binding sites per lobe, only one functional Ca2+ binding site operates in the amino-terminus. To understand this light chain substitution, we used hydrogen-deuterium exchange mass spectrometry (HDX-MS) to examine dynamic changes in ACaM and CaM upon Ca2+ binding and interaction with the two CaM binding motifs of myosin VI (insert2 and IQ motif). HDX-MS reveals that binding of Ca2+ to ACaM destabilizes its N-lobe but stabilizes the entire C-lobe, whereas for CaM, Ca2+ binding induces a pattern of alternating stabilization/destabilization throughout. The conformation of this stable holo-C-lobe of ACaM seems to be a "prefigured" version of the conformation adopted by the holo-C-lobe of CaM for binding to insert2 and the IQ motif of myosin VI. Strikingly, the interaction of holo-ACaM with either peptide converts the holo-N-lobe to its Ca2+-free, more stable, form. Thus, ACaM in vivo should bind the myosin VI light chain sites in an apo-N-lobe/holo-C-lobe state that cannot fulfill the Ca2+-related functions of holo-CaM required for myosin VI motor assembly and activity. These findings indicate that inhibition of myosin VI motor activity is a precondition for transition to an anchoring function.

Specific patterns of endogenous functional connectivity are associated with harm avoidance in OCD.

BACKGROUND: Individuals with OCD show persistent-avoidance behaviors, often in the absence of actual threat. Quality-of-life costs and heterogeneity support the need for novel brain-behavior intervention targets. Informed by mechanistic and anatomic studies of persistent-avoidance in rodents and non-human primates, our goal was to test whether connections within a hypothesized persistent-avoidance related network predicted OCD-related harm-avoidance (HA), a trait measure of persistent-avoidance. We hypothesized that 1)HA, not OCD diagnosis, would be associated with altered endogenous connectivity in at least one connection in the network; 2)HA-specific findings would be robust to comorbid symptoms; and 3)reliable findings would replicate in an holdout testing subsample. METHODS: Using resting-state fcMRI, cross-validated elastic-net for feature selection and Poisson generalized linear models, we tested which connections significantly predicted HA in our training subsample(n=73;71.8% Female;nHC=36,nOCD=37); robustness to comorbidities; and replicability in a testing subsample(n=30;56.7% Female;nHC=15,nOCD=15). RESULTS: Stronger inverse connectivity between right dorsal anterior cingulate and right basolateral-amygdala (R_dACC-R_BLA) and stronger positive connectivity between right ventral anterior insula and left ventral-striatum (R_vaIns-L_VS) were associated with greater HA across groups. Network connections did not discriminate OCD diagnosis or predict HA-correlated traits, suggesting sensitivity to trait HA. The dACC-BLA relationship was robust to controlling for comorbidities and medication in individuals with OCD and was also predictive of HA in our testing subsample. CONCLUSION: Stronger inverse dACC-BLA connectivity was robustly and reliably associated with HA across groups and in OCD. Results support the relevance of a cross-species persistent-avoidance-related network to OCD, with implications for precision-based approaches and treatment.

MET receptor serves as a promising target in melanoma brain metastases.

The development of brain metastases hallmarks disease progression in 20-40% of melanoma patients and is a serious obstacle to therapy. Understanding the processes involved in the development and maintenance of melanoma brain metastases (MBM) is critical for the discovery of novel therapeutic strategies. Here, we generated transcriptome and methylome profiles of MBM showing high or low abundance of infiltrated Iba1high tumor-associated microglia and macrophages (TAMs). Our survey identified potential prognostic markers of favorable disease course and response to immune checkpoint inhibitor (ICi) therapy, among them APBB1IP and the interferon-responsive gene ITGB7. In MBM with high ITGB7/APBB1IP levels, the accumulation of TAMs correlated significantly with the immune score. Signature-based deconvolution of MBM via single sample GSEA revealed enrichment of interferon-response and immune signatures and revealed inflammation, stress and MET receptor signaling. MET receptor phosphorylation/activation maybe elicited by inflammatory processes in brain metastatic melanoma cells via stroma cell-released HGF. We found phospho-METY1234/1235 in a subset of MBM and observed a marked response of brain metastasis-derived cell lines (BMCs) that lacked druggable BRAF mutations or developed resistance to BRAF inhibitors (BRAFi) in vivo to MET inhibitors PHA-665752 and ARQ197 (tivantinib). In summary, the activation of MET receptor in brain colonizing melanoma cells by stromal cell-released HGF may promote tumor self-maintenance and expansion and might counteract ICi therapy. Therefore, therapeutic targeting of MET possibly serves as a promising strategy to control intracranial progressive disease and improve patient survival.

Photobiomodulation CME Part I: Overview and Mechanism of Action.

Photobiomodulation (PBM), previously known as low-level laser light therapy, represents a non-invasive form of phototherapy that utilizes wavelengths in the red light (RL, 620-700 nm) portion of the visible light (VL, 400-700 nm) spectrum and the near-infrared (NIR, 700-1440 nm) spectrum. PBM is a promising and increasingly used therapy for the treatment of various dermatologic and non-dermatologic conditions. Photons from RL and NIR are absorbed by endogenous photoreceptors including mitochondrial cytochrome C oxidase (COX). Activation of COX leads to the following changes: modulation of mitochondrial adenosine triphosphate (ATP), generation of reactive oxygen species (ROS), and alterations in intracellular calcium levels. The associated modulation of ATP, ROS and calcium levels promotes the activation of various signaling pathways (e.g., insulin-like growth factors, phosphoinositide 3-kinase pathways), which contribute to downstream effects on cellular proliferation, migration and differentiation. Effective PBM therapy is dependent on treatment parameters (e.g., fluence, treatment duration and output power). PBM is generally well-tolerated and safe with erythema being the most common and self-limiting adverse cutaneous effect.

Educational Programme on Knowledge, Attitudes, and Practice of Oral Care/Hygiene Provision by Healthcare Providers to Older Residents in Long-Term Care Institutions: A Case-Control Study.

BACKGROUND: Much attention has been paid to advocate proper oral care/hygiene provision by healthcare providers in long-term care institutions (LTCIs). This study aimed to evaluate the effects of an oral health education (OHE) programme (intervention) on knowledge, attitudes, and practice (KAP) of healthcare providers in providing oral care/hygiene to older residents in LTCIs. METHODS: A case control study was conducted at two LTCIs, with one assigned as the intervention group and the other as the control group. A KAP survey was administered before and after the intervention, and oral status was assessed by standardized clinical photographs taken before and after oral hygiene provision on three older residents. RESULTS: A total of 40 healthcare providers (20 in intervention and 20 in control groups) participated, with the attitudes and overall KAP significantly improved in the intervention group after the OHE programme. Interestingly, the knowledge of those in the control LTCI was significantly declined at re-evaluation (mean scores were from 17.25 to 14.30), indicating inadequate oral health and care training despite having more experience in taking care of older people. Significant differences in practice were observed between the two groups after the OHE programme (p = 0.006). The three older residents exhibited poor oral health and multiple oral problems. CONCLUSIONS: This study revealed that the OHE programme effectively improved attitudes of the healthcare providers and provided a sustaining effect on attitude towards oral health and oral care. However, there were still inadequacies in oral hygiene provision by some healthcare providers, possibly due to unattended oral diseases and hygiene needs, as well as personal and environmental barriers that merit further investigation. Regular evaluation and enforcement of oral care/hygiene provision in LTCIs are necessary to maintain oral health and prevent dental and gum diseases in older residents. Immediate referral for dental treatment is recommended for older people with signs of dental/oral disease(s).

Neural markers of mania that distinguish inpatient adolescents with bipolar disorder from those with other psychopathology.

Pediatric bipolar disorder (BD) is difficult to distinguish from other psychiatric disorders, a challenge which can result in delayed or incorrect interventions. Using neuroimaging we aimed to identify neural measures differentiating a rarified sample of inpatient adolescents with BD from other inpatient psychopathology (OP) and healthy adolescents (HC) during a reward task. We hypothesized reduced subcortical and elevated cortical activation in BD relative to other groups, and that these markers will be related to self-reported mania scores. We examined inpatient adolescents with diagnosis of BD-I/II (n = 29), OP (n = 43), and HC (n = 20) from the Inpatient Child and Adolescent Bipolar Spectrum Imaging study. Inpatient adolescents with BD showed reduced activity in right thalamus, left thalamus, and left amygdala, relative to inpatient adolescents with OP and HC. This reduced neural function explained 21% of the variance in past month and 23% of the variance in lifetime mania scores. Lower activity in regions associated with the reward network, during reward processing, differentiates BD from OP in inpatient adolescents and explains >20% of the variance in mania scores. These findings highlight potential targets to aid earlier identification of, and guide new treatment developments for, pediatric BD.