Harvard Medical School

BACKGROUND: Specific components of independent and interdependent self-construal have been associated with psychopathology. However, most studies on this topic have been cross-sectional, precluding causal inferences. We used contemporaneous and temporal cross-lagged network analysis to establish weak causal influences in understanding the association between self-construal and psychopathology components. METHODS: Middle-aged and older community-dwelling adults (n = 3,294) participated in the Midlife Development in the United States study across two time-points, spaced nine years apart. Six self-construal (interdependence: connection to others, commitment to others, receptiveness to influence; independence: behavioral consistency, sense of difference from others, self-reliance) and three psychopathology nodes (major depressive disorder (MDD), generalized anxiety disorder (GAD), and panic disorder (PD) symptom severity) were examined. All network analyses controlled for age, sex, race, and number of chronic illnesses as covariates. RESULTS: Contemporaneous and temporal networks yielded relations between elevated MDD and PD and increased receptiveness to influence. Heightened GAD symptom severity was associated with future increased difference from others and decreased connection to others, commitment to others, and receptiveness to influence. Higher MDD, GAD, and PD severity were associated with future lower self-reliance. Network comparison tests revealed no consistent network differences across sex and race. LIMITATIONS: DSM-III-R measures of MDD, GAD, and PD were used. Results may not generalize to culturally diverse racial groups. CONCLUSIONS: Changes in self-construal may result from increased MDD, GAD, and PD severity. Findings suggest the importance of targeting common mental health symptoms to positively influence how individuals view the self and others in various social contexts.

Purpose Sexual minority (SM; e.g., gay, lesbian, bisexual) individuals are disproportionately impacted by alcohol and other drug (AOD) use disorders and psychosocial factors that can exacerbate AOD use disorders and hinder recovery. This study examines SM sub-group differences (monosexual [gay/lesbian] versus bisexual) regarding adaptation to recovery measured by indices of psychosocial functioning. Identifying differential needs of gay/lesbian versus bisexual individuals could improve services to better meet the needs of SM individuals in recovery. Methods Using data from the National Recovery Study, a nationally representative cross-sectional sample of US adults who reported resolving an AOD problem (N = 2,002), we compared heterosexual to monosexual and bisexual SM individuals on socio-demographic characteristics, AOD use and treatment, and psychosocial variables. Results Bisexual individuals were significantly younger than heterosexual individuals (p = .002 and p ≤ 0.001 among men and women, respectively) and reported significantly fewer years since AOD problem resolution compared to heterosexual individuals (p = .004 and p = .003 among men and women, respectively). Most notably, bisexual individuals, but not gay/lesbian individuals, reported significantly lower quality of life (QOL), happiness, self-esteem, and significantly higher distress compared to heterosexual individuals. Conclusion Bisexual, but not monosexual, SM individuals in recovery from an AOD use disorder, were younger and reported worse psychosocial functioning than heterosexual individuals. Findings highlight significant differences between monosexual versus bisexual identified individuals with a notable disadvantage experienced by bisexual individuals. More needs to be learned about the challenges faced by bisexual individuals in recovery to better address their needs and support long-term AOD recovery.

Introduction More brands are using tobacco-free nicotine (TFN) in electronic cigarettes (e-cigarettes) and these products are becoming increasingly popular. The term TFN and claims about its properties can mislead consumers about the harms and addictiveness of TFN e-cigarettes, which may increase initiation of these products among non-smokers or influence current smokers’ decisions to adopt TFN e-cigarettes as a harm reduction measure. Methods We conducted an observational, cross-sectional survey of 777 adolesc aged 13–17 and 655 current adult cigarette smokers residing in Massachusetts, Connecticut, New Hampshire, Rhode Island, or Vermont about their TFN e-cigarette awareness, use, perceptions, and susceptibility. We examined the association between prior awareness of TFN and use, perceptions, and susceptibility. Results One-third of adolescents and adults reported being aware of TFN. TFN e-cigarette use was less common than tobacco-derived nicotine (TDN) e-cigarette use among adolescents (8.9 % vs. 30.5 %) and adults (21.1 % vs. 79.4 %). Compared to unaware adolescents, adolescents who were aware of TFN more frequently reported being more likely to use TFN compared to TDN e-cigarettes and that TFN e-cigarettes are more addictive than those containing TDN. Aware adult smokers more frequently reported that TFN e-cigarettes are more addictive than TDN e-cigarettes, TFN e-cigarettes cause some harm, TDN e-cigarettes cause little harm, and that TFN and TDN e-cigarettes are equally harmful than those who were unaware previously. Conclusion Public health education campaigns are needed to educate consumers about the harms and addictiveness of TFN e-cigarettes.

Psychotherapies are first-line treatments for most mental disorders, but their absolute outcomes (i.e., response and remission rates) are not well studied, despite the relevance of such information for health care users, providers and policy makers. We aimed to examine absolute and relative outcomes of psychotherapies across eight mental disorders: major depressive disorder (MDD), social anxiety disorder, panic disorder, generalized anxiety disorder (GAD), specific phobia, post-traumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), and borderline personality disorder (BPD). We used a series of living systematic reviews included in the Metapsy initiative (www. metapsy.org), with a common strategy for literature search, inclusion of studies and extraction of data, and a common format for the analyses. Literature search was conducted in major bibliographical databases (PubMed, PsycINFO, Embase, and the Cochrane Register of Controlled Trials) up to January 1, 2023. We included randomized controlled trials comparing psychotherapies for any of the eight mental disorders, established by a diagnostic interview, with a control group (waitlist, care-as-usual, or pill placebo). We conducted random-effects model pairwise meta-analyses. The main outcome was the absolute rate of response (at least 50% symptom reduction between baseline and post-test) in the treatment and control conditions. Secondary outcomes included the relative risk (RR) of response, and the number needed to treat (NNT). Random-effects meta-analyses of the included 441 trials (33,881 patients) indicated modest response rates for psychotherapies: 0.42 (95% CI: 0.39-0.45) for MDD; 0.38 (95% CI: 0.33-0.43) for PTSD; 0.38 (95% CI: 0.30-0.47) for OCD; 0.38 (95% CI: 0.33-0.43) for panic disorder; 0.36 (95% CI: 0.30-0.42) for GAD; 0.32 (95% CI: 0.29-0.37) for social anxiety disorder; 0.32 (95% CI: 0.23-0.42) for specific phobia; and 0.24 (95% CI: 0.15-0.36) for BPD. Most sensitivity analyses broadly supported these findings. The RRs were significant for all disorders, except BPD. Our conclusion is that most psychotherapies for the eight mental disorders are effective compared with control conditions, but absolute response rates are modest. More effective treatments and interventions for those not responding to a first-line treatment are needed.

Objective Although hand synovitis is prevalent in the older population, the etiology remains unclear. Hyperuricemia, a modifiable metabolic disorder, may serve as an underlying mechanism of hand synovitis, but little is known about their relationship. We assessed the association between hyperuricemia and hand synovitis in a large population‐based sample. Methods We performed a cross‐sectional study in Longshan County, Hunan Province, China. Hyperuricemia was defined as a serum urate level >420 μmol/L in men and >360 μmol/L in women. Ultrasound examinations were performed on both hands of 4,080 participants, and both gray‐scale synovitis and the Power Doppler signal (PDS) were assessed using semiquantitative scores (grades 0–3). We evaluated the association of hyperuricemia with hand gray‐scale synovitis (grade ≥2) and PDS (grade ≥1), respectively, adjusting for age, sex, and body mass index. Results All required assessments for analysis were available for 3,286 participants. The prevalence of hand gray‐scale synovitis was higher among participants with hyperuricemia (30.0%) than those with normouricemia (23.3%), with an adjusted odds ratio (aOR) of 1.28 (95% confidence interval [CI] 1.00–1.62). Participants with hyperuricemia also had a higher prevalence of PDS (aOR 2.36; 95% CI 1.15–4.81). Furthermore, hyperuricemia positively associated, both at the hand and joint levels, with the presence of gray‐scale synovitis (aOR 1.27; 95% CI 1.00–1.60 and adjusted prevalence ratio [aPR] 1.26; 95% CI 1.10–1.44, respectively) and PDS (aOR 2.35; 95% CI 1.15–4.79 and aPR 2.34; 95% CI 1.28–4.30, respectively). Conclusion This population‐based study provides more evidence for a positive association between hyperuricemia and prevalent hand synovitis.

The development of novel compounds for tissue-specific targeting and imaging is often impeded by a lack of lead compounds and the availability of reliable chemistry. Automated chemical synthesis systems provide a potential solution by enabling reliable, repeated access to large compound libraries for screening. Here we report an integrated solid-phase combinatorial chemistry system created using commercial and customized robots. Our goal is to optimize reaction parameters, such as varying temperature, shaking, microwave irradiation, aspirating and dispensing large-sized solid beads, and handling different washing solvents for separation and purification. This automated system accommodates diverse chemical reactions such as peptide synthesis and conventional coupling reactions. To confirm its functionality and reproducibility, 20 nerve-specific contrast agents for biomedical imaging were systematically and repeatedly synthesized and compared to other nerve-targeted agents using molecular fingerprinting and Uniform Manifold Approximation and Projection, which lays the foundation for creating reliable and reproductive chemical libraries in bioimaging and nanomedicine.

The primary cilium is a characteristic feature of most non‐immune cells and functions as an environmental signal transduction sensor. The defects in primary cilium have profound effects on the developmental program, including the maturation of retinal epithelium. The ciliary length is tightly regulated during ciliogenesis, but the impact of inflammation on ciliary length remains elusive. The current study investigates the outcome of inflammatory stimuli for the primary cilium length in retinal epithelium cells and mouse embryonic fibroblasts. Here, we report that exposure to the pro‐inflammatory cytokine TNF‐alpha elongates cilia in a mixed‐lineage kinase (MLK)‐dependent manner. Pro‐inflammatory stimuli such as bacterial LPS and interferon‐gamma have similar effects on ciliary length. In contrast, febrile condition‐mimicking heat stress dramatically reduced the number of ciliated cells regardless of TNF‐alpha exposure but did not shorten TNF‐induced elongation, suggesting distinct but rapid effects of inflammatory stresses on ciliogenesis.

Disease Overview Plasmablastic lymphoma (PBL) is a rare CD20‐negative aggressive lymphoma with a poor prognosis under standard treatment options. Though PBL is associated with human immunodeficiency virus infection and other immunosuppressed states, it can also affect immunocompetent individuals. Diagnosis The diagnosis requires a high clinical suspicion and pathological confirmation. EBER expression and MYC gene rearrangements are frequently detected. The differential diagnosis includes EBV+ diffuse large B‐cell lymphoma, extracavitary primary effusion lymphoma, ALK+ DLBCL, and HHV8+ large B‐cell lymphoma, among others. Risk Stratification Age ≥60 years, advanced clinical stage, and high intermediate and high International Prognostic Index scores are associated with worse survival. Management Combination chemotherapy regimens, such as EPOCH, are recommended. The addition of bortezomib, lenalidomide, or daratumumab might improve outcomes. Including PBL patients and their participation in prospective clinical trials is warranted.

Purpose Peripheral nerve stimulation (PNS) limits the usability of state‐of‐the‐art whole‐body and head‐only MRI gradient coils. We used detailed electromagnetic and neurodynamic modeling to set an explicit PNS constraint during the design of a whole‐body gradient coil and constructed it to compare the predicted and experimentally measured PNS thresholds to those of a matched design without PNS constraints. Methods We designed, constructed, and tested two actively shielded whole‐body Y‐axis gradient coil winding patterns: YG1 is a conventional symmetric design without PNS‐optimization, whereas YG2's design used an additional constraint on the allowable PNS threshold in the head‐imaging landmark, yielding an asymmetric winding pattern. We measured PNS thresholds in 18 healthy subjects at five landmark positions (head, cardiac, abdominal, pelvic, and knee). Results The PNS‐optimized design YG2 achieved 46% higher average experimental thresholds for a head‐imaging landmark than YG1 while incurring a 15% inductance penalty. For cardiac, pelvic, and knee imaging landmarks, the PNS thresholds increased between +22% and +35%. For abdominal imaging, PNS thresholds did not change significantly between YG1 and YG2 (−3.6%). The agreement between predicted and experimental PNS thresholds was within 11.4% normalized root mean square error for both coils and all landmarks. The PNS model also produced plausible predictions of the stimulation sites when compared to the sites of perception reported by the subjects. Conclusion The PNS‐optimization improved the PNS thresholds for the target scan landmark as well as most other studied landmarks, potentially yielding a significant improvement in image encoding performance that can be safely used in humans.

Ebstein anomaly (EA) is a rare congenital heart defect characterized by abnormal development of the tricuspid valve (TV) and right ventricular myocardium. This study documents 2 dramatic cases of fetal EA characterized by hydrops and cardiomegaly, leading to intrauterine or early neonatal death. These clinical outcomes were associated with morphological abnormalities including severe tricuspid regurgitation, unguarded TV orifice, pulmonary atresia, and flattened right ventricular myocardium. This study highlights that these adverse anatomical features may result in unfavorable clinical outcomes in fetal EA. While timely identification of such features by prenatal ultrasound is crucial for providing accurate prognostic stratification and guiding treatment decisions, fetopsy may be necessary to discern EA among the spectrum of right-heart anomalies.

INTRODUCTION Sleep disturbances are common in Alzheimer's disease (AD) and may reflect pathologic changes in brain networks. To date, no studies have examined changes in sleep functional connectivity (FC) in AD or their relationship with network hyperexcitability and cognition. METHODS We assessed electroencephalogram (EEG) sleep FC in 33 healthy controls, 36 individuals with AD without epilepsy, and 14 individuals with AD and epilepsy. RESULTS AD participants showed increased gamma connectivity in stage 2 sleep (N2), which was associated with longitudinal cognitive decline. Network hyperexcitability in AD was associated with a distinct sleep connectivity signature, characterized by decreased N2 delta connectivity and reversal of several connectivity changes associated with AD. Machine learning algorithms using sleep connectivity features accurately distinguished diagnostic groups and identified “fast cognitive decliners” among study participants who had AD. DISCUSSION Our findings reveal changes in sleep functional networks associated with cognitive decline in AD and may have implications for disease monitoring and therapeutic development. Highlights Brain functional connectivity (FC) in Alzheimer's disease is altered during sleep. Sleep FC measures correlate with cognitive decline in AD. Network hyperexcitability in AD has a distinct sleep connectivity signature.

Few studies have proved that bioprinting itself helps recapitulate native tissue functions mainly because the bioprinted macro shape can rarely, if ever, influence cell function. This can be more problematic in bioprinting cartilage, generally considered more challenging to engineer. Here a new method is shown to micro‐pattern chondrocytes within bioprinted sub‐millimeter micro tissues, denoted as patterned micro‐articular‐cartilages tissues (PA‐MCTs). Under the sole influence of bioprinted cellular patterns. A pattern scoring system is developed after over 600 bioprinted cellular patterns are analyzed. The top‐scored pattern mimics that of the isogenous group in native articular cartilage. Under the sole influence of this pattern during PA‐MCTs bio‐assembling into macro‐cartilage and repairing cartilage defects, chondrogenic cell phenotype is preserved, and cartilagenesis is initiated and maintained. Neocartilage tissues from individual and assembled PA‐MCTs are comparable to native articular cartilage and superior to cartilage bioprinted with homogeneously distributed cells in morphology, biochemical components, cartilage‐specific protein and gene expression, mechanical properties, integration with host tissues, zonation forming and stem cell chondrogenesis. PA‐MCTs can also be used as osteoarthritic and healthy cartilage models for therapeutic drug screening and cartilage development studies. This cellular patterning technique can pave a new way for bioprinting to recapitulate native tissue functions via tissue genesis.

Background: To analyze the clinical course and outcomes of autoimmune vs. non-autoimmune surgi-cally induced scleral necrosis (SISN).Methods: Multicentric, retrospective, comparative cohort study. Eighty-two eyes of 70 patients with SISN were classified according to pathogenic mechanism into autoimmune vs. non-autoimmune. Main out-come measures included necrosis onset, type of surgery, associated systemic disease, visual acuity, and treatment were analysed in patients followed for ≥ 6 months.Results: Forty-six (65.7%) patients were women, and the median age was 66 (range: 24–90) years. Most patients (82.9%) had unilateral disease. The median time between surgery and SISN onset was 58 (1–480) months. Thirty-one (37.8%) eyes were classified as autoimmune, and 51 (62.2%) as non-autoimmune SISN. Autoimmune SISN was associated with a shorter time between the surgical procedure and SISN onset than non-autoimmune cases (median of 26 vs. 60 months, p = 0.024). Also, autoimmune SISN was associated with cataract extraction (93.5% vs. 25.5%, p < 0.001), severe scleral inflammation (58.1% vs. 17.6%, p < 0.001), and higher incidence of ocular complications (67.7% vs. 33.3%, p = 0.002) than non- autoimmune cases. Remission was achieved with medical management alone in 44 (86.3%) eyes from the non-autoimmune and in 27 (87.1%) from the autoimmune group (p = 0.916). Surgical management was required in 11 (13.4%) eyes, including two requiring enucleations due to scleral perforation and phthisis bulbi.Conclusions: Eyes with autoimmune SISN had a higher rate of cataract surgery, severe scleral inflammation, and ocular complications. Early SISN diagnosis and appropriate management, based on clinical features and pathogenic mechanisms, are critical to avoid sight-threatening complications.

This correspondence talks about advancing neurorehabilitation intervention to enhance neurodevelopmental outcomes in pediatric patients following encephalocele resection

The travoprost intracameral implant was recently approved by the US Food and Drug Administration for sustained release medical treatment of open-angle glaucoma in the USA. The approval represents a substantial and progressive step forward in the area of sustained-release glaucoma therapy. Topical intraocular pressure-lowering medications for the treatment of glaucoma are faced with a host of challenges for long-term and usually lifelong care. A changing paradigm in glaucoma management involves first-line interventions with laser modalities, micro-invasive surgeries, and sustained-release treatment platforms. Future needs in the area of sustained-release therapy include a non-prostaglandin drug delivery platform and longer-term treatments that do not require surgical reintervention.

Positron emission tomography (PET) is a noninvasive molecular imaging technique that utilizes biologically active radiolabeled compounds to image biochemical processes. As such, PET can provide important pathophysiological information associated with pain of different etiologies. Consequently, the information obtained using PET often combined with magnetic resonance imaging or computed tomography can provide useful information for diagnosing and monitoring changes associated with pain. This review covers the most important PET tracers that have been used to image pain including tracers for fundamental biological processes such as glucose metabolism and cerebral blood flow, to receptor‐specific tracers such as ion channels and neurotransmitters. For each tracer, we describe the structure and radiochemical synthesis of the tracer followed by a brief summary of the available preclinical and clinical studies. By providing a summary of the PET tracers that have been employed for PET imaging of pain, this review aims to serve as a reference for preclinical, translational, and clinical investigators interested in molecular imaging of pain. Finally, the review ends with an outlook of the needs and opportunities in this area.