Centering and flourishing: an online intervention study assessing the effects of a Christian contemplative practice on stress-reduction and human flourishing.

Despite widespread engagement in contemplative religious practices, comparatively little research has been conducted on their potential effects on well-being. Furthermore, few studies have focused on how an explicitly religious framing may impact the outcomes of such practices. In this online randomized controlled trial (N = 702), we tested the well-being effects of a contemplative prayer practice called Centering Prayer on self-identifying Christians. We compared 1) presenting the practice with an explicitly religious framing (experimental condition), 2) presenting the practice without an explicitly religious framing (active control), and 3) presenting simple instructions to reflect on the day, without any instructions regarding a meditation-like practice (passive control). After randomization into one of these three conditions, participants were asked to complete their assigned practice daily for 28 days. We hypothesized that the religious framing version of the practice would increase well-being over the active and passive control conditions. Well-being was assessed at three follow-up time points: one day, one week, and one month after the practice period. We found no group differences between the conditions on our primary outcome measure of well-being at one-week post-intervention. Each group increased in well-being from baseline to follow-up. We found significant group differences on acute measures of spiritual experience, the Mystical Experience Questionnaire (MEQ-30) and Daily Spiritual Experience Questionnaire (DSES). These results suggest that a religious framing may not enhance well-being effects but may alter spiritual outcomes related to contemplative practices.

Caregiver burden and its sociodemographic determinants in family caregivers of patients with schizophrenia attending a psychiatric tertiary hospital in South Africa.

Background: Chronic mental illnesses such as schizophrenia affect patients' functioning, making caregiving necessary although burdensome. Aim: This study aimed to determine caregiver burden and its sociodemographic determinants in family caregivers of patients with schizophrenia attending a Psychiatric Outpatient Department (POD). Setting: Tertiary hospital in Northern Pretoria, South Africa. Methods: In this cross-sectional study conducted over 3 months, 300 consecutive family caregivers who attended the POD were administered a 22-item Zarit Burden Interview (ZBI-22), which has a score of 0-88, with higher values indicating more burden. Their sociodemographic characteristics were ascertained. Linear and ordinal logistic regression analyses were performed to identify determinants or predictors of total and severe burdens, respectively. Results: Most caregivers were aged 46.0 ± 14 years, females (62%), parents (39%), of low-income status (93.7%), had secondary education (70%), resided with the patient (87%), and helped with all troublesome activities (95.3%). The median ZBI-22 score was 19.0 (interquartile range: 13.0-30.5). The determinants of both total and severe burdens were: caregiver age ≥ 50 years adjusted odds ratio (aOR): 2.55, confidence interval (CI): 1.49-4.36; residential area farther away from the hospital aOR: 1.76, CI: 1.3-2.99; increasing months of caregiving aOR: 1.0, CI: 1.001-1.009, p = 0.006; and not having another family member that needs care aOR: 0.43, CI: 0.24-0.78. Conclusion: Having mental healthcare facilities close to residential areas and assisting caregivers aged ≥ 50 years who have multiple family members who need care may alleviate the burden. Contribution: Predicting total and severe caregiver burdens contemporaneously is effective for identifying potential burden interventions.

Sleep Disruption Precedes Forebrain Synaptic Tau Burden and Contributes to Cognitive Decline in a Sex-Dependent Manner in the P301S Tau Transgenic Mouse Model.

Sleep disruption and impaired synaptic processes are common features in neurodegenerative diseases, including Alzheimer's disease (AD). Hyperphosphorylated Tau is known to accumulate at neuronal synapses in AD, contributing to synapse dysfunction. However, it remains unclear how sleep disruption and synapse pathology interact to contribute to cognitive decline. Here, we examined sex-specific onset and consequences of sleep loss in AD/tauopathy model PS19 mice. Using a piezoelectric home-cage monitoring system, we showed PS19 mice exhibited early-onset and progressive hyperarousal, a selective dark-phase sleep disruption, apparent at 3 months in females and 6 months in males. Using the Morris water maze test, we report that chronic sleep disruption (CSD) accelerated the onset of decline of hippocampal spatial memory in PS19 males only. Hyperarousal occurs well in advance of robust forebrain synaptic Tau burden that becomes apparent at 6-9 months. To determine whether a causal link exists between sleep disruption and synaptic Tau hyperphosphorylation, we examined the correlation between sleep behavior and synaptic Tau, or exposed mice to acute or chronic sleep disruption at 6 months. While we confirm that sleep disruption is a driver of Tau hyperphosphorylation in neurons of the locus ceruleus, we were unable to show any causal link between sleep loss and Tau burden in forebrain synapses. Despite the finding that hyperarousal appears earlier in females, female cognition was resilient to the effects of sleep disruption. We conclude sleep disruption interacts with the synaptic Tau burden to accelerate the onset of cognitive decline with greater vulnerability in males.

Relative foveal dark adaptation: a potential method for assessing macular health.

BACKGROUND/OBJECTIVE: Dark adaptation measures photoreceptor recovery following intense light stimulation. Time to recovery reflects retinal function. We describe a novel method of relative foveal dark adaptation using an iPhone. Data from a small number of healthy subjects were studied to assess reproducibility, effects of age, and consider potential clinical utility. METHODS: Relative foveal dark adaption was studied in 6 normal subjects across ages from 20 to 81 years and across differing testing conditions. Foveal bleaching is produced by fixating a bright white circle on an iPhone for variable times. After foveal bleaching an annular surround appears to complete a bullseye stimulus with surround initially brighter than centre. As the fovea recovers the centre regains brightness. Relative foveal dark adaptation, the time for the visual anchor to shift from surround to centre, was studied across a range of bleaching times, ages, and testing conditions. RESULTS: Dispersion of dark adaptation times grows with increasing age. Foveal bleaching for 30 s was as effective as longer times. Testing times with a 30 s bleach were less than 1 min. Foveal dark adaptation was reproducible within each subject and was unaffected by ambient room lighting, pupil size, and light attenuation. Repeat, immediately sequential testing was similarly reproducible except after long bleaching. CONCLUSIONS: This method of dark adaptation is intuitive, repeatable, and relatively unaffected by testing condition. Testing times are brief, requiring only an iPhone screen positioned at reading distance. Relative foveal dark adaptation may be a useful tool to assess macular health.

Minimally invasive surgical approach to model hypertrophic scarring in the rabbit ear.

BACKGROUND: Current strategies for hypertrophic scar prevention and treatment are limited. OBJECTIVE: To facilitate these efforts, a minimally invasive hypertrophic scar model was created in a rabbit ear for the first time based on previous methods used to induce ischemia. METHODS: Six New Zealand white rabbits (12 ears total) were studied. First, ischemia was achieved by ligating the cranial artery, cranial vein and central artery, while preserving the caudal artery, caudal vein and central vein, respectively. The relative level of ischemia induced at time of surgery, both baseline and maximum perfusion, was assessed with a fluorescent light-assisted angiography and demonstrated lower rates of perfusion in the ischemic ears. Following vascular injury, a 2-cm full thickness linear wound was created on the ventral ear and closed with 4 - 0 Nylon sutures under high tension. For each rabbit, one ear received a combination of ischemia and wounding with suture tension (n = 6), while the other ear was non-ischemic with wounding and suture tension alone (n = 6). RESULTS: Four weeks post-operatively, ischemic ears developed scar hypertrophy (histological scar thickness: 1.1 ± 0.2 mm versus 0.5 ± 0.1 mm, p < 0.05). CONCLUSION: Herein, we describe a novel, prototypical minimally invasive rabbit ear model of hypertrophic scar formation that can allow investigation of new drugs for scar prevention.

Glioma-derived M-CSF and IL-34 license M-MDSCs to suppress CD8+ T cells in a NOS-dependent manner.

Glioblastoma (GBM) is the most common malignant primary brain tumor, resulting in poor survival despite aggressive therapies. GBM is characterized by a highly heterogeneous and immunosuppressive tumor microenvironment (TME) made up predominantly of infiltrating peripheral immune cells. One significant immune cell type that contributes to glioma immune evasion is a population of immunosuppressive cells, termed myeloid-derived suppressor cells (MDSCs). Previous studies suggest that a subset of myeloid cells, expressing monocytic (M)-MDSC markers and dual expression of chemokine receptors CCR2 and CX3CR1, utilize CCR2 to infiltrate the TME. This study evaluated the mechanism of CCR2+/CX3CR1+ M-MDSC differentiation and T cell suppressive function in murine glioma models. We determined that bone marrow-derived CCR2+/CX3CR1+ cells adopt an immune suppressive cell phenotype when cultured with glioma-derived factors. Glioma secreted CSF1R ligands M-CSF and IL-34 were identified as key drivers of M-MDSC differentiation while adenosine and iNOS pathways were implicated in M-MDSC suppression of T cells. Mining a human GBM spatial RNAseq database revealed a variety of different pathways that M-MDSCs utilize to exert their suppressive function that are driven by complex niches within the microenvironment. These data provide a more comprehensive understanding of the mechanism of M-MDSCs in glioblastoma.

Ancillary immunohistochemical and molecular testing in the classification of cutaneous sweat gland/duct neoplasms: A validation study with emphasis on histomorphologic correlation and pathological diagnosis.

Sweat gland neoplasms represent a challenging area of dermatopathology, as they are relatively uncommon and often histopathologically complex. Recent studies have uncovered distinct immunohistochemical and molecular profiles in several sweat gland neoplasms, including digital papillary adenocarcinoma (DPA), papillary eccrine adenoma/tubular apocrine adenoma (PEA/TAA), poroid family tumors (PFT)/porocarcinoma, and clear cell hidradenoma (CCH)/clear cell hidradenocarcinoma (CCHCa). To further evaluate the diagnostic utility of ancillary studies in various sweat gland neoplasms, we performed an independent validation study in a cohort of patients with acral and non-acral tumors (9 DPA, 8 PEA/TAA, 13 PFT, 5 porocarcinoma, 23 CCH, 7 CCHCa, 6 sweat gland carcinoma not otherwise specified). p63 immunohistochemistry (IHC) demonstrated a myoepithelial pattern in 8/8 DPA and 4 of 4 tested PEA/TAA cases, and showed a ductal pattern in all tested PFT/porocarcinoma and CCH/CCHCa cases (42/42). All PEA/TAA (8/8) cases were positive for BRAF V600E IHC. 5 of 12 tested PFT and 5/5 porocarcinoma cases showed either positive staining with NUT IHC or harbored YAP1::NUTM1 fusion gene by RNA sequencing. MAML2 fluorescence in situ hybridization (FISH) was positive in all CCH and CCHCa cases (23/23 and 7/7, respectively). Our results further support the usefulness of appropriate ancillary studies in precise classification of sweat gland tumors, which may be routinely applied in diagnostic pathology practice when morphologic evaluation is in doubt.

Nivolumab With or Without Ipilimumab Combined with Stereotactic Body Radiotherapy in patients with Metastatic Biliary Tract Cancer: A Randomized Phase 2 Study.

PURPOSE: Evaluate the clinical benefits of nivolumab with/without ipilimumab combined with stereotactic body radiotherapy (SBRT) in patients with pretreated metastatic biliary tract cancer (mBTC). EXPERIMENTAL DESIGN: The study was a phase 2 randomized trial with Simon's optimal 2-stage design requiring 36 evaluable patients per group after second stage. Sixty-one patients were included from September 2018 to January 2022 and randomized (1:1) to receive SBRT (15 Gy × 1 on day one to a primary or metastatic lesion) and nivolumab (3 mg/kg intravenously on day one and every 2 weeks) with/without ipilimumab (1 mg/kg intravenously on day one and every 6 weeks). Primary endpoint was clinical benefit rate (CBR), defined as the percentage of patients with complete response, partial response or stable disease. Decision to continue accrual into the second stage depended on CBR from first stage. RESULTS: Forty-two patients received SBRT/nivolumab/ipilimumab with a CBR of 31.0% (95% CI, 17.6-47.1). Five patients (11.9%) achieved partial response with median duration of 4.4 months (range, 1.1-21.5). Nineteen patients received SBRT/nivolumab. This group was closed after the initial stage based on a CBR of 10.5% (95% CI, 1.3-33.1). Adverse events were graded with National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Grade ≥3 treatment-related adverse events occurred in 13 (31%) and 3 (16%) patients in the SBRT/nivolumab/ipilimumab and SBRT/nivolumab groups, respectively. One patient died from immune-related hepatitis in the SBRT/nivolumab/ipilimumab group. CONCLUSION: Combining SBRT, nivolumab and ipilimumab is well tolerated, feasible, and shows response in a subgroup of patients with mBTC.

Affimer reagents as tool molecules to modulate platelet GPVI-ligand interactions and specifically bind GPVI dimer.

Glycoprotein (GP)VI plays a key role in collagen-induced platelet aggregation. Affimers are engineered binding protein alternatives to antibodies. We screened and characterized GPVI-binding Affimers as novel tools to probe GPVI function. Among the positive clones, M17, D22 and D18 bound GPVI with the highest affinities (KD in the nM range). These Affimers inhibited GPVI-CRP-XL/collagen interactions, CRP-XL/collagen induced platelet aggregation and D22 also inhibited in vitro thrombus formation on a collagen surface under flow. D18 bound GPVI dimer but not monomer. GPVI binding was increased for D18 but not M17/D22 upon platelet activation by CRP-XL and ADP. D22 but not M17/D18 displaced nanobody2 (Nb2) binding to GPVI, indicating similar epitopes for D22 with Nb2 but not for M17/D18. Mapping of binding sites revealed that D22 binds a site that overlaps with Nb2 on the D1-domain, while M17 targets a site on the D2-domain, overlapping in part with the glenzocimab binding site, a humanized GPVI antibody Fab-fragment. D18 targets a new region on the D2-domain. We found that D18 is a stable non-covalent dimer and forms a stable complex with dimeric GPVI with 1:1 stoichiometry. Taken together, our data demonstrate that Affimers modulate GPVI-ligand interactions and bind different sites on GPVI D1/D2-domains. D18 is dimer-specific and could be used as a tool to detect GPVI dimerization or clustering in platelets. A dimeric epitope regulating ligand binding was identified on the GPVI D2-domain, which could be used for the development of novel bivalent antithrombotic agents selectively targeting GPVI dimer on platelets.

Alcohol Misuse post Metabolic and Bariatric Surgery: A Systematic Review of Longer-term Studies with Focus on new Onset Alcohol use Disorder and Differences Between Surgery Types.

BACKGROUND: Evidence suggests an increased risk of alcohol problems post-surgery where no problematic alcohol use was present prior to surgery which may be different across types of surgery. OBJECTIVE: To characterise the risk of new onset alcohol misuse post bariatric surgery, differences between surgeries and the impact over time. METHODS: All published studies on new and relapsing alcohol use were reviewed. Data were classed as 'subjective' (clinical interview, self-report questionnaires) and 'objective' (hospital admissions, substance misuse programmes) and further categorised by follow up time - 'shorter-term' (one year), 'medium-term' (one year to two years) and 'long-term' (> two years). RESULTS: Twenty-three of the forty-two studies included in the review reported new onset data. Nine studies reported on differences between surgery types. In those reporting objective measures, all of which were long term, RYGB carried a higher risk than SG, followed by LAGB. All but one study using subjective measures reported a small but significant number of new onset concerning alcohol use, and comparisons between surgery types had more varied results than the objective measures. Studies of substance abuse programmes found high rates of new onset cases (17-60%). CONCLUSION: This systematic review provides support for the consensus guidance suggesting patients should be informed of a small but significant risk of new onset alcohol use following bariatric surgery, with the strongest evidence in the medium- to long-term and in those who have had RYGB followed by SG.

Cognitive Functioning in Youth with Anxiety Disorders: A Systematic Review.

Anxiety disorders are disorders involving cognition. Research on cognition in youth with anxiety can focus on cognitive content (e.g., self-talk) as well cognitive functioning. The present review examines domains of cognitive functioning (i.e., episodic memory, language, attention, executive functioning, motor skills, and visual functioning) in youth diagnosed with an anxiety disorder. A database search of Embase, PsycINFO, and PubMed yielded 28 studies that met inclusion criteria of youth aged 17 years or younger, a sample diagnosed with a principal anxiety disorder and a comparison sample of controls, a comparison between those samples, and use of a behavioral measure of neuropsychological performance. Findings did not identify any cognitive functioning strengths for anxious youth. Deficits were found in two domains (i.e., receptive language and motor skills) whereas no deficits were found in attention, visuospatial skills and one domain of executive functioning (i.e., inhibition). Most domains had mixed findings. Additional analysis indicated that anxiety disorders in youth are not associated with diminished IQ. Directions for future research are identified including (a) the prioritization of studies with larger, representative samples (b) the role of cognitive functioning as a predictor of anxiety treatment outcome (c) the examination of the effect of treatment on cognitive performance, and (d) the course of anxiety and potential impairment in cognitive functioning.

Risk Factors for Atraumatic Medial Patellar Facet Lesions.

Background: Medial patellar facet lesions have been well-described in the setting of patellar instability. However, relatively little is known about risk factors for atraumatic medial patellar facet lesions. Purpose/Hypothesis: To identify clinical and radiographic risk factors for medial patellar facet lesions in patients without a history of trauma or patellar instability. It was hypothesized that a posterior tibial tubercle relative to the trochlear groove would be a risk factor for atraumatic medial patellar facet lesions. Study Design: Case-control study; Level of evidence, 3. Methods: A total of 37 patients with atraumatic medial patellar facet lesions were matched by age, sex, and body mass index with 37 control patients without a history of patellofemoral dysplasia. Demographic and imaging characteristics were compared between groups. Plain radiography was used to evaluate Wiberg type, and magnetic resonance imaging was used to calculate Caton-Deschamps index, tibial tubercle-trochlear groove distance, trochlear facet asymmetry ratio, patellotrochlear index, sulcus depth, patellar bisect ratio, and tibial tubercle height. Statistically significant variables from univariate analysis were used as inputs to the multivariate regression model to assess independent risk factors. Results: There were no differences between groups with respect to Wiberg type, Caton-Deschamps index, tibial tubercle-trochlear groove distance, sulcus depth, or patellotrochlear index (P > .05 for all). The medial facet lesion group had a larger medial trochlear facet (trochlear facet asymmetry ratio, 0.72 ± 0.11 vs 0.60 ± 0.09; P < .001), a more medial-lying patella in the trochlear groove (patellar bisect ratio, 0.57 ± 0.06 vs 0.55 ± 0.07; P = .035), and a more posterior tibial tubercle relative to the trochlear groove (tibial tubercle height, -3.13 ± 5.21 vs -0.23 ± 5.93 mm; P = .030) compared with the control group. Multivariate regression analysis identified trochlear facet asymmetry and tibial tubercle height as independent risk factors for medial patellar facet lesions (relative risk = 97.3 [95% CI, 14.9-635.1], P < .001 and relative risk = 0.95 [95% CI, 0.92-0.98], P = .004, respectively). Conclusion: A relatively larger medial trochlear facet and a more posterior tibial tubercle relative to the trochlear groove were found to be risk factors for medial patellar facet lesions in patients without a history of trauma or patellar instability.

Organisms have gravity: taking an organism-centered approach in experimental biology.

When you take the time to observe another organism, there is a sort of gravity that can take hold, a mixture of curiosity and connection that expands and strengthens the more you interact with that organism. Yet, in research, a connection with one's study organism can, at times, feel countercultural. Study organisms are sometimes viewed more as tools to conveniently study biological questions. Here, we explicitly highlight the importance of organism-centered research not only in scientific discovery, but also in conservation and in the communication and perception of science.

Facilitating Seed Iron Uptake through Amine-Epoxide Microgels: A Novel Approach to Enhance Cucumber (Cucumis sativus) Germination.

Enhancing the initial stages of plant growth by using polymeric gels for seed priming presents a significant challenge. This study aimed to investigate a microgel derived from polyetheramine-poly(propylene oxide) (PPO) and a bisepoxide (referred to as micro-PPO) as a promising alternative to optimize the seed germination process. The micro-PPO integrated with an iron micronutrient showed a positive impact on seed germination compared with control (Fe solutions) in which the root length yield improved up to 39%. Therefore, the element map by synchrotron-based X-ray fluorescence shows that the Fe intensities in the seed primers with the micro-PPO-Fe gel are about 3-fold higher than those in the control group, leading to a gradual distribution of Fe species through most internal embryo tissues. The use of micro-PPO for seed priming underscores their potential for industrial applications due to the nontoxicity results in zebrafish assays and environmentally friendly synthesis of the water-dispersible monomers employed.

Multidisciplinary surgical considerations for en bloc resection of sacral chordoma: review of recent advances and a contemporary single-center series.

OBJECTIVE: Contemporary management of sacral chordomas requires maximizing the potential for recurrence-free and overall survival while minimizing treatment morbidity. En bloc resection can be performed at various levels of the sacrum, with tumor location and volume ultimately dictating the necessary extent of resection and subsequent tissue reconstruction. Because tumor resection involving the upper sacrum may be quite destabilizing, other pertinent considerations relate to instrumentation and subsequent tissue reconstruction. The primary aim of this study was to survey the surgical approaches used for managing primary sacral chordoma according to location of lumbosacral spine involvement, including a narrative review of the literature and examination of the authors' institutional case series. METHODS: The authors performed a narrative review of pertinent literature regarding reconstruction and complication avoidance techniques following en bloc resection of primary sacral tumors, supplemented by a contemporary series of 11 cases from their cohort. Relevant surgical anatomy, advances in instrumentation and reconstruction techniques, intraoperative imaging and navigation, soft-tissue reconstruction, and wound complication avoidance are also discussed. RESULTS: The review of the literature identified several surgical approaches used for management of primary sacral chordoma localized to low sacral levels (mid-S2 and below), high sacral levels (involving upper S2 and above), and high sacral levels with lumbar involvement. In the contemporary case series, the majority of cases (8/11) presented as low sacral tumors that did not require instrumentation. A minority required more extensive instrumentation and reconstruction, with 2 tumors involving upper S2 and/or S1 levels and 1 tumor extending into the lower lumbar spine. En bloc resection was successfully achieved in 10 of 11 cases, with a colostomy required in 2 cases due to rectal involvement. All 11 cases underwent musculocutaneous flap wound closure by plastic surgery, with none experiencing wound complications requiring revision. CONCLUSIONS: The modern management of sacral chordoma involves a multidisciplinary team of surgeons and intraoperative technologies to minimize surgical morbidity while optimizing oncological outcomes through en bloc resection. Most cases present with lower sacral tumors not requiring instrumentation, but stabilizing instrumentation and lumbosacral reconstruction are often required in upper sacral and lumbosacral cases. Among efforts to minimize wound-related complications, musculocutaneous flap closure stands out as an evidence-based measure that may mitigate risk.

Effectiveness of a two-component nutritional strategy for blood pressure control in individuals with hypertension users of a public health system: a randomized controlled clinical trial.

OBJECTIVE: To evaluate the effectiveness of a nutritional strategy based on two components and adapted for the public health system on blood pressure, cardiometabolic features, self-care, qualify of life and diet quality in individuals with hypertension. METHODS: NUPRESS was an open-label, parallel-group, superiority randomized controlled clinical trial in which participants at least 21 years with hypertension and poorly controlled blood pressure were randomly assigned (1 : 1 allocation ratio) to either an individualized dietary prescription according to nutritional guidelines (control group, n  = 205); or a two-component nutrition strategy, including a goal-directed nutritional counseling and mindfulness techniques (NUPRESS [intervention] group, n  = 205). Primary outcomes were SBP (mmHg) after 24 weeks of follow up and blood pressure control, defined as either having SBP more than 140 mmHg at baseline and achieving 140 mmHg or less after follow-up or having SBP 140 mmHg or less at baseline and reducing the frequency of antihypertensive drugs in use after follow-up. RESULTS: In total, 410 participants were randomized and submitted to an intention-to-treat analysis regarding primary outcomes. Both groups decreased blood pressure, but after adjusting for baseline values, there was no significant difference between them on SBP [intervention-control difference: -0.03 (-3.01; 2.94); P  = 0.98] nor blood pressure control [odds ratio 1.27 (0.82; 1.97); P  = 0.28]. No differences between groups were also detected regarding secondary and tertiary outcomes. CONCLUSION: There was no difference between a two-component nutritional strategy and an established dietary intervention on blood pressure in participants with hypertension.

Dynamic analyses of a soft tissue-implant interface: Biological responses to immediate versus delayed dental implants.

AIM: To qualitatively and quantitatively evaluate the formation and maturation of peri-implant soft tissues around 'immediate' and 'delayed' implants. MATERIALS AND METHODS: Miniaturized titanium implants were placed in either maxillary first molar (mxM1) fresh extraction sockets or healed mxM1 sites in mice. Peri-implant soft tissues were evaluated at multiple timepoints to assess the molecular mechanisms of attachment and the efficacy of the soft tissue as a barrier. A healthy junctional epithelium (JE) served as positive control. RESULTS: No differences were observed in the rate of soft-tissue integration of immediate versus delayed implants; however, overall, mucosal integration took at least twice as long as osseointegration in this model. Qualitative assessment of Vimentin expression over the time course of soft-tissue integration indicated an initially disorganized peri-implant connective tissue envelope that gradually matured with time. Quantitative analyses showed significantly less total collagen in peri-implant connective tissues compared to connective tissue around teeth around implants. Quantitative analyses also showed a gradual increase in expression of hemidesmosomal attachment proteins in the peri-implant epithelium (PIE), which was accompanied by a significant inflammatory marker reduction. CONCLUSIONS: Within the timeframe examined, quantitative analyses showed that connective tissue maturation never reached that observed around teeth. Hemidesmosomal attachment protein expression levels were also significantly reduced compared to those in an intact JE, although quantitative analyses indicated that macrophage density in the peri-implant environment was reduced over time, suggesting an improvement in PIE barrier functions. Perhaps most unexpectedly, maturation of the peri-implant soft tissues was a significantly slower process than osseointegration.

Facile synthesis of diiodoheteroindenes and understanding their Sonogashira cross-coupling selectivity for the construction of unsymmetrical enediynes.

Electrophile-promoted cyclizations of functionalized alkynes offer a useful tool for constructing halogen-substituted heterocycles primed for further derivatization. Preinstallation of an iodo-substituent at the alkyne prior to iodo-cyclization opens access to ortho di-iodinated heterocyclic precursors for the preparation of unsymmetrical heterocycle-fused enediynes. This general approach was used to prepare 2,3-diiodobenzothiophene, 2,3-diiodoindole, and 2,3-diiodobenzofuran, a useful family of substrates for systematic studies of the role of heteroatoms on the regioselectivity of cross-coupling reactions. Diiodobenzothiophene showed much higher regioselectivity for Sonogashira cross-coupling at C2 than diiodoindole and diiodobenzofuran. As a result, benzothiophene can be conveniently involved in a one-pot sequential coupling with two different alkynes, yielding unsymmetrical benzothiophene-fused enediynes. On the other hand, the Sonogashira reaction of diiodoindole and diiodobenzofuran formed considerable amounts of di-substituted enediynes in addition to the monoalkyne product by coupling at C2. Interestingly, no C3-monocoupling products were observed for all of the diiodides, suggesting that the incorporation of the 1st alkyne at C2 activates the C3 position for the 2nd coupling. Additional factors affecting regioselectivity were detected, discussed and connected, through computational analysis, to transmetalation being the rate-determining step for the Sonogashira reaction. Several enediynes synthesized showed cytotoxic activity, which is not associated with DNA strand breaks typical of natural enediyne antibiotics.

Is the A-1 Pigment in Photosystem I Part of P700? A (P700+-P700) FTIR Difference Spectroscopy Study of A-1 Mutants.

The involvement of the second pair of chlorophylls, termed A-1A and A-1B, in light-induced electron transfer in photosystem I (PSI) is currently debated. Asparagines at PsaA600 and PsaB582 are involved in coordinating the A-1B and A-1A pigments, respectively. Here we have mutated these asparagine residues to methionine in two single mutants and a double mutant in PSI from Synechocystis sp. PCC 6803, which we term NA600M, NB582M, and NA600M/NB582M mutants. (P700+-P700) FTIR difference spectra (DS) at 293 K were obtained for the wild-type and the three mutant PSI samples. The wild-type and mutant FTIR DS differ considerably. This difference indicates that the observed changes in the (P700+-P700) FTIR DS cannot be due to only the PA and PB pigments of P700. Comparison of the wild-type and mutant FTIR DS allows the assignment of different features to both A-1 pigments in the FTIR DS for wild-type PSI and assesses how these features shift upon cation formation and upon mutation. While the exact role the A-1 pigments play in the species we call P700 is unclear, we demonstrate that the vibrational modes of the A-1A and A-1B pigments are modified upon P700+ formation. Previously, we showed that the A-1 pigments contribute to P700 in green algae. In this manuscript, we demonstrate that this is also the case in cyanobacterial PSI. The nature of the mutation-induced changes in algal and cyanobacterial PSI is similar and can be considered within the same framework, suggesting a universality in the nature of P700 in different photosynthetic organisms.