Relationship between Abnormal Spontaneous Brain Activity and Altered Neuromuscular Activation of Lumbar Paraspinal Muscles in Chronic Low Back Pain.

OBJECTIVE: To investigate the neural mechanism underlying functional reorganization and motor coordination strategies in patients with chronic low back pain (cLBP). DESIGN: A case-control study based on data collected during routine clinical practice. SETTING: This study was conducted at the the First Affiliated Hospital of Sun Yat-sen University. PARTICIPANTS: Fifteen patients with cLBP and fifteen healthy controls. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Whole brain blood oxygen level-dependent signals were measured using functional magnetic resonance imaging and amplitude of low-frequency fluctuation (ALFF) method to identify pain-induced changes in regional spontaneous brain activity. A novel approach based on the surface electromyography (EMG) system and fine-wire electrodes was used to record EMG signals in the deep multifidus, superficial multifidus, and erector spinae. RESULTS: In cLBP, compared with healthy groups, ALFF was higher in the medial prefrontal, primary somatosensory, primary motor, and inferior temporal cortices, whereas it was lower in the cerebellum and anterior cingulate and posterior cingulate cortices. Furthermore, the decrease in the average EMG activity of three lumbar muscles in the cLBP group was positively correlated with the ALFF values of the primary somatosensory cortex, motor cortex, precuneus, and middle temporal cortex but significantly negatively correlated with the ALFF values of the medial prefrontal and inferior temporal cortices. Interestingly, the correlation between the functional activity in the cerebellum and the EMG activity varied in the lumbar muscles. CONCLUSIONS: These findings suggest a functional association between changes in spontaneous brain activity and altered voluntary neuromuscular activation patterns of the lumbar paraspinal muscles, providing new insights into the mechanisms underlying pain chronicity as well as important implications for developing novel therapeutic targets of cLBP.

Geographic access to cardiac rehabilitation and cardiovascular disease outcomes: A study of rural United States counties.

Prior studies have examined rural-urban disparities in access to cardiac rehabilitation (CR). However, few have examined the relationship between disparate access to CR and cardiovascular disease outcomes in rural areas. In this analysis of 1975 nonmetro United States counties, we investigated the relationship between number of hospitals with CR and Medicare-population hospitalization rates (per 1000 adults ≥65 years) and county-population mortality rates (per 100,000 adults ≥18 years) due to coronary heart disease (CHD), heart failure (HF), or stroke, using multivariable linear-regression-modeling adjusting for socio-demographic and comorbid conditions. Median CHD hospitalization (13.0 vs. 12.2), HF hospitalization (16.1 vs. 13.3), HF death (114.2 vs. 110.9), stroke hospitalization (12.0 vs. 10.9), and stroke death (39.6 vs. 37.1) rates were higher in nonmetro counties without versus with a CR facility (p-values< 0.001). There were inverse correlations between number of hospitals with CR and CHD (r= -0.161), HF (r= -0.261) and stroke (r= -0.237) hospitalization rates, and stroke mortality (r= -0.144) rates (p-values< 0.001). After adjustment, as the number of hospitals with CR increased, there were decreases in hospitalization rates of 1.78 for CHD, 7.20 for HF, and 2.43 for stroke, per 1000 in the population (p-values < 0.001) and decreases in stroke deaths of 9.17 per 100,000 in the population (p= 0.02). Access to hospitals with CR in US nonmetro counties is inversely related to CHD, HF, and stroke hospitalization, and stroke mortality. Our findings call for reducing barriers to CR in nonmetro communities and further exploring the relationship between CR and stroke outcomes.

[Analysis of a Chinese pedigree with Bw subtype due to a novel variant of α-1,3-N-acetylgalactosaminyltransferase gene].

OBJECTIVE: To explore the serological characteristics and genetic variant in a Chinese pedigree with Bw subtype. METHODS: A 32-year-old female proband who had undergone prenatal examination on December 10, 2020 at the 960th Hospital of the PLA Joint Logistics Support Force and five members from her pedigree were selected as the study subjects. Peripheral blood samples were collected and subjected to ABO blood group phenotyping with serological methods and ABO blood group genotyping with fluorescent PCR. Genetic testing and haplotype analysis were carried out by direct sequencing of the entire coding region of the ABO gene in the proband and cloned sequencing of exons 1-7. RESULTS: The blood type serology of the proband showed Bw, and her ABO blood type genotype determined by fluorescence PCR was B/O. The direct sequencing results showed that the proband had matched the ABO*O.01.01/ABO*B.01 genotype and carried a c.1A>G variant. Cloned sequencing has confirmed the c.1A>G variant to have occurred in the ABO*B.01 allele. Family analysis revealed that the mother of the proband had an O blood type, her husband had a B phenotype, and her three children had a normal B blood type. DNA sequencing showed that the two sons of the proband had a genotype of ABO*B.01 and c.1A>G/ABO*B.01. The daughter of the proband was ABO*O.01.01/ABO*B.01, whilst her mother was ABO*O.01.01/ABO *O.01.02. The novel c.1A>G variant sequence has been registered with the database with a number MZ076785 1. CONCLUSION: The novel c.1A>G variant of exon 1 of α- 1,3 galactose aminotransferase gene probably underlay the reduced expression of B antigen in this pedigree.

Isocyanide-Based Multicomponent Reaction: Cascade α-Acyloxylation/Carboxamidation and [3 + 1+1] Cyclization of I(III)/S(VI)-Ylides.

A metal-free cascade of α-acyloxylation/carboxamidation of I(III)/S(VI)-ylides, carboxylic acids, and isonitriles via a Passerini-like multicomponent reaction is reported. Unexpectedly, [3 + 1+1] cyclization involving I(III)/S(VI)-ylides and two molecules of ethyl isocyanoacetate was observed. The strategy allows for the synthesis of unsymmetrical α,α-disubstituted ketones and functionalized pyrroles with up to 99% yield and wide substrate compatibility. Notably, the procedure has been extended to the late-stage modification of drugs and natural products, offering an elegant complement to the classic Passerini reaction.

Time to Dementia Diagnosis Among Veterans with Comorbid Insomnia and Depressive Episodes.

Background: Older adults with heart failure are at elevated risk of Alzheimer's disease and related dementias (AD/ADRD). Research suggests that insomnia and depressive episodes contribute somewhat dissociable impacts on risk for AD/ADRD in this patient population, although the temporal ordering of effects is unknown. Objective: This study examined time to dementia diagnosis among patients with comorbid insomnia and/or depressive episodes in an epidemiological sample. Methods: Secondary data analyses were conducted using a cohort study of 203,819 Veterans with a primary admission diagnosis of heart failure in 129 VA Medical Centers. Results: Patients with diagnoses of both insomnia and depressive episodes had the shortest time to a dementia diagnosis at both 1-year (Hazard ratio = 1.43, 95% CI [1.36, 1.51]) and 3-year follow-up time points (Hazard ratio = 1.40, 95% CI [1.34, 1.47]) versus patients with one or neither comorbidity. Conclusions: Individuals with both comorbidities had the shortest time to dementia onset. Screening for these comorbidities may help to identify patients at elevated risk of dementia who could benefit from enhanced monitoring or early intervention strategies for more rapid detection and management of dementia symptoms.

Risk factors for reoperation after discectomy of lumbar herniated intervertebral disc disease.

Objectives: Discectomy is the most common surgery for lumbar herniated intervertebral disc (HIVD) disease. However, 5%-24% of patients undergo a second surgery due to recurrent disc herniation. Materials and Methods: This study was aimed to identify the risk factors for reoperation after discectomy of lumbar HIVD and recommend treatment for patients with a high risk of reoperation. We recruited patients diagnosed as having single-level lumbar HIVD who underwent open discectomy from January 1, 2000, to December 31, 2012 in our hospital. We used a survival curve to inspect the survival time and reoperation rate after surgery. We discussed the correlation of reoperation rate with discectomy level, body mass index, heavy lifting after surgery, sex, and age. Furthermore, we investigated the correlation between the experience of a surgeon and the reoperation rate. Results: A total of 619 patients were enrolled in our study. Most patients were 40-60 years old (48.8%), and most of them had herniation at L4/5 level (48.9%). The 8-year survival rate was 92%. Weight lifting after surgery may increase the reoperation rate by 115 and 18 times for those >60 years and <40 years, respectively. In addition, less experience of the surgeon and female sex had a high reoperation rate. Conclusion: Postoperative working modification may be very important for preventing patients from recurrent HIVD. For elderly people with HIVD, a more conservative therapy could be selected. If patients with lumbar spine hypermobility or severe degeneration require wide laminectomy, primary fusion should be considered.

Adipose-derived stem cells and antibiotics: A novel synergistic approach for treating implant-related osteomyelitis.

Implant-related osteomyelitis poses a significant challenge in orthopedic practice, particularly due to the increasing prevalence of antibiotic-resistant infections and biofilm-associated complications. This article focused on exploring the potential of combination therapy with adipose-derived stem cells (ADSCs) and antibiotics to overcome these challenges, thereby enhancing treatment efficacy. A systematic synthesis of the results of recent in vivo studies, predominantly those using rat models, was performed. Studies that evaluated the effectiveness of ADSCs combined with antibiotics against common pathogens in implant-related osteomyelitis, particularly Staphylococcus aureus and methicillin-resistant Staphylococcus epidermidis, were selected. A significant reduction in symptoms such as swelling, abscess formation, and bacterial burden in the ADSCs + antibiotic-treated group was observed in all studies. In addition, microcomputed tomography revealed reduced osteolysis, indicating enhanced bone preservation. Furthermore, histological examination revealed improved tissue structure and altered immune response, signifying the dual role of ADSCs in enhancing antibiotic action and modulating the immune system. This review highlights the promising role of the concurrent use of ADSCs and antibiotics in the treatment of implant-related osteomyelitis. This novel therapeutic strategy has the potential to revolutionize the management of complex orthopedic infections, especially those resistant to conventional treatments. However, further research is required to translate the results of animal studies into clinical applications and to develop optimized treatment protocols for human use.

Define Critical Parameters of Trastuzumab-Mediated ADCC Assays via Assay Optimization Processes, Focusing on the Impact of Cryopreserved Effector Cells on Assay Performance.

The mechanisms of mAb-induced ADCC have been well established. However, the ADCC bioassays used to quantify mAb-induced ADCC require continued development/refinement to properly assess and compare the potency of newly developed therapeutic mAbs and biosimilars to meet regulatory requirements. We used trastuzumab and a lactate dehydrogenase (LDH)-based ADCC bioassay as a model to define critical parameters of the ADCC bioassay, describing how several bioassay parameters, including preparation of effector cells, E/T ratio, target cell selection, bioassay media components, and treatment time can influence the data quality of the ADCC activity. We confirm that a 4 to 24 h recovery cultivation is required to restore peripheral blood mononuclear cells (PBMCs) and natural killer (NK) cell activity toward ADCC when using cryopreserved PBMCs. Furthermore, we delineated the cellular mechanisms underlying the restored ADCC activity following the recovery cultivation. We observed that CD69, an early marker of NK cell activation, was upregulated and a new subset CD56dim/CD16dim population was dramatically increased in the recovered NK cells, which led to an increase in expression and secretion of perforin, granzyme B, and cytokine production. This study provides comprehensive technical insights into ADCC bioassay optimization to inform trastuzumab biosimilar development. The knowledge gained from this study can also be leveraged to guide bioassay development for therapeutic mAbs with ADCC as the primary mechanism of action.

Radial extracorporeal shockwave promotes osteogenesis-angiogenesis coupling of bone marrow stromal cells from senile osteoporosis via activating the Piezo1/CaMKII/CREB axis.

Radial extracorporeal shockwave (r-ESW) and bone marrow stromal cells (BMSCs) have been reported to alleviate senile osteoporosis (SOP), but its regulatory mechanism remains unclear. In this study, we firstly isolated human BMSCs from bone marrow samples and treated with varying r-ESW doses. And we found that r-ESW could enhance the proliferation of SOP-BMSCs in a dose-dependent manner by EdU assay. Subsequently, the impact of r-ESW on the proliferation, apoptosis and multipotency of BMSCs was assessed. And the outcomes of flow cytometry, Alizarin red S (ARS), and tube formation test demonstrated that the optimal shockwave obviously boosted SOP-BMSCs osteogenesis and angiogenesis but exhibited no significant impact on cell apoptosis. Additionally, the signaling of Piezo1 and CaMKII/CREB was examined by Western blotting, qPCR and immunofluorescence. And the results showed that r-ESW promoted the expression of Piezo1, increased intracellular Ca2+ and activated the CaMKII/CREB signaling pathway. Then, the application of Piezo1 siRNA hindered the r-ESW-induced enhancement ability of osteogenesis coupling with angiogenesis of SOP-BMSCs. The use of the CaMKII/CREB signaling pathway inhibitor KN93 suppressed the Piezo1-induced increase in osteogenesis and angiogenesis in SOP-BMSCs. Finally, we also found that r-ESW might alleviate SOP in the senescence-accelerated mouse prone 6 (SAMP6) model by activating Piezo1. In conclusion, our research offers experimental evidence and an elucidated underlying molecular mechanism to support the use of r-ESW as a credible rehabilitative treatment for senile osteoporosis.

Reconstruction of Defects After Oral Cancer Surgery With the Superior Thyroid Artery Perforator Flap.

OBJECTIVE: The superior thyroid artery perforator flap (STAPF) was previously presented as a type of locoregional pedicled flap for lateral facial and temple defects. In this study, we aimed to present our clinical experience with this flap for the reconstruction of soft tissue defects after oral cancer surgery. METHODS: From February 2019 to December 2022, 24 patients with oral cancers at the School and Hospital of Stomatology, Peking University were included. Among these patients, 10 had cancers located in the tongue, five in the cheek inside the oral cavity, three in the lower gingiva, two in the upper gingiva, two in the floor of the mouth, and two in the palate. All patients were treated with extended tumor resection, neck dissection, and STAPFs to reconstruct the soft tissue defects. The details of the flap, including the flap size, venous flow, vascular pedicle length, the attatched muscle, and operation time were evaluated. RESULTS: The dimensions of the flap skin paddle ranged from 3 cm × 5 cm to 6 × 14 cm. Fourteen patients had a closely concomitant superior thyroid vein perforator. Ten patients had non-closely concomitant superior thyroid veins perforators which retrograde external jugular vein. The vascular pedicle length ranged from 5 to 9 cm. The infrahyoid muscle group or sternocleidomastoid muscle was included in the flaps in three patients. A total of 23/24 flaps were successful. CONCLUSIONS: The STAPF is a viable reconstructive option for patients with oral cancers. It has the advantages of being robust, being thin, short operation time, and minor donor site complications. LEVEL OF EVIDENCE: 4 Laryngoscope, 2024.

Pharmacokinetics, safety, and efficacy of Fuqi Guben Gao in the treatment of kidney-yang deficiency syndrome: a randomized, double-blind phase I trial.

Introduction: Fuqi Guben Gao (FQGBG) is a botanical drug formulation composed of FuZi (FZ; Aconitum carmichaelii Debeaux [Ranunculaceae; Aconiti radix cocta]), Wolfberry (Lycium barbarum L. [Solanaceae; Lycii fructus]), and Cinnamon (Neolitsea cassia (L.) Kosterm. [Lauraceae; Cinnamomi cortex]). It has been used to clinically treat nocturia caused by kidney-yang deficiency syndrome (KYDS) for over 30 years and warms kidney yang. However, the pharmacological mechanism and the safety of FQGBG in humans require further exploration and evaluation. Methods: We investigated the efficacy of FQGBG in reducing urination and improving immune organ damage in two kinds of KYDS model rats (hydrocortisone-induced model and natural aging model), and evaluated the safety of different oral FQGBG doses through pharmacokinetic (PK) parameters, metabonomics, and occurrence of adverse reactions in healthy Chinese participants in a randomized, double-blind, placebo-controlled, single ascending dose clinical trial. Forty-two participants were allocated to six cohorts with FQGBG doses of 12.5, 25, 50, 75, 100, and 125 g. The PKs of FQGBG in plasma were determined using a fully validated LC-MS/MS method. Results: FQGBG significantly and rapidly improved the symptoms of increased urination in both two KYDS model rats and significantly resisted the adrenal atrophy in hydrocortisone-induced KYDS model rats. No apparent increase in adverse events was observed with dose escalation. Major adverse drug reactions included toothache, thirst, heat sensation, gum pain, diarrhea, abdominal distension, T-wave changes, and elevated creatinine levels. The PK results showed a higher exposure level of benzoylhypaconine (BHA) than benzoylmesaconine (BMA) and a shorter half-life of BMA than BHA. Toxic diester alkaloids, aconitine, mesaconitine, and hypaconitine were below the lower quantitative limit. Drug-induced metabolite markers primarily included lysophosphatidylcholines, fatty acids, phenylalanine, and arginine metabolites; no safety-related metabolite changes were observed. Conclusion: Under the investigated dosing regimen, FQGBG was safe. The efficacy mechanism of FQGBG in treating nocturia caused by KYDS may be related to the improvement of the hypothalamus-pituitary-adrenal axis function and increased energy metabolism. Clinical Trial Registration: https://www.chictr.org.cn/showproj.html?proj=26934, identifier ChiCTR1800015840.

Study on the impact of comprehensive geriatric assessment on anxiety and depression in chronic obstructive pulmonary disease patients.

BACKGROUND: Psychological factors such as anxiety and depression will not only aggravate the symptoms of chronic obstructive pulmonary disease (COPD) patients and reduce the quality of life of patients, but also affect the treatment effect and long-term prognosis. Therefore, it is of great significance to explore the clinical application of senile comprehensive assessment in the treatment of COPD and its influence on psychological factors such as anxiety and depression. AIM: To explore the clinical application of comprehensive geriatric assessment in COPD care and its impact on anxiety and depression in elderly patents. METHODS: In this retrospective study, 60 patients with COPD who were hospitalized in our hospital from 2019 to 2020 were randomly divided into two groups with 30 patients in each group. The control group was given routine nursing, and the observation group was given comprehensive assessment. Clinical symptoms, quality of life [COPD assessment test (CAT) score], anxiety and depression Hamilton Anxiety Rating Scale (HAMA) and Hamilton Depression Rating Scale (HAMD) were compared between the two groups. RESULTS: CAT scores in the observation group decreased from an average of 24.5 points at admission to an average of 18.3 points at discharge, and in the control group from an average of 24.7 points at admission to an average of 18.3 points at discharge. The average score was 22.1 (P < 0.05). In the observation group, HAMA scores decreased from 14.2 points at admission to 8.6 points at discharge, and HAMD scores decreased from 13.8 points at admission to 7.4 points at discharge. The mean HAMD scores in the control group decreased from an average of 14.5 at admission to an average of 12.3 at discharge, and from an average of 14.1 at admission to an average of 11.8 at discharge. CONCLUSION: The application of comprehensive geriatric assessment in COPD care has a significant effect on improving patients' clinical symptoms and quality of life, and can effectively reduce patients' anxiety and depression.

Probing the Structural and Electronic Properties of the Anionic and Neutral Tellurium-Doped Boron Clusters TeBnq (n = 3-16, q = 0, -1).

In this study, we employ density functional theory along with the artificial bee colony algorithm for cluster global optimization to explore the low-lying structures of TeBnq (n = 3-16, q = 0, -1). The primary focus is on reporting the structural properties of these clusters. The results reveal a consistent doping pattern of the tellurium atom onto the in-plane edges of planar or quasi-planar boron clusters in the most energetically stable isomers. Additionally, we simulate the photoelectron spectra of the cluster anions. Through relative stability analysis, we identify three clusters with magic numbers -TeB7-, TeB10, and TeB12. The aromaticity of these clusters is elucidated using adaptive natural density partitioning (AdNDP) and magnetic properties analysis. Notably, TeB7- exhibits a perfect σ-π doubly aromatic structure, while TeB12 demonstrates strong island aromaticity. These findings significantly contribute to our understanding of the structural and electronic properties of these clusters.

Membrane protein MHZ3 regulates the on-off switch of ethylene signaling in rice.

Ethylene regulates plant growth, development, and stress adaptation. However, the early signaling events following ethylene perception, particularly in the regulation of ethylene receptor/CTRs (CONSTITUTIVE TRIPLE RESPONSE) complex, remains less understood. Here, utilizing the rapid phospho-shift of rice OsCTR2 in response to ethylene as a sensitive readout for signal activation, we revealed that MHZ3, previously identified as a stabilizer of ETHYLENE INSENSITIVE 2 (OsEIN2), is crucial for maintaining OsCTR2 phosphorylation. Genetically, both functional MHZ3 and ethylene receptors prove essential for OsCTR2 phosphorylation. MHZ3 physically interacts with both subfamily I and II ethylene receptors, e.g., OsERS2 and OsETR2 respectively, stabilizing their association with OsCTR2 and thereby maintaining OsCTR2 activity. Ethylene treatment disrupts the interactions within the protein complex MHZ3/receptors/OsCTR2, reducing OsCTR2 phosphorylation and initiating downstream signaling. Our study unveils the dual role of MHZ3 in fine-tuning ethylene signaling activation, providing insights into the initial stages of the ethylene signaling cascade.

Emotional contagion and cognitive empathy regulate the effect of depressive symptoms on empathy-related brain functional connectivity in patients with chronic back pain.

BACKGROUND: Chronic pain and depression share common neural mechanisms, but their impacts on empathy are different. It is unclear how comorbid depressive symptoms affect empathy-related brain function in patients with chronic pain. METHODS: A total of 29 healthy participants and 107 patients with chronic back pain (CBP) were included in this study. All subjects underwent a functional MRI scan with concurrent empathic stimulation. Multiple linear regression, moderation analysis, and mediation analysis were used to explore the impacts of chronic pain and comorbid depression on empathy. RESULTS: The interaction between the pain intensity and the depressive symptoms affected the functional connectivity (FC) of the insula-middle frontal gyrus (MFG), and the severity of the self-rating depression scale (SDS) scores moderated the effect of the pain on the left insula-left MFG FC. Within the CBP group, the emotional contagion (EC) scores served as a mediator in the association between the SDS scores and the FC of the left middle cingulate cortex (MCC)-inferior temporal gyrus (ITG), and the level of cognitive empathy (CE) moderated the effect of the SDS scores on the left MCC-ITG FC. LIMITATIONS: There is a lack of research on the effects of depressive symptoms on empathy in individuals with different types of chronic pain. CONCLUSION: Depressive symptoms were strongly associated with the emotional contagion in patients with chronic back pain. Furthermore, the emotional contagion and the cognitive empathy regulated the effect of the comorbid depressive symptoms on the MCC-ITG connectivity in patients with chronic back pain.

Structural and functional characterization of IgG- and non-IgG-based T-cell-engaging bispecific antibodies.

Bispecific T-cell-engaging antibodies are a growing class of therapeutics with numerous molecules being tested in clinical trials and, currently, seven of them have received market approval. They are structurally complex and function as adaptors to redirect the cytotoxicity of T cells to kill tumor cells. T-cell-engaging bispecific antibodies can be generally divided into two categories: IgG/IgG-like and non-IgG-like formats. Different formats may have different intrinsic potencies and physiochemical properties, and comprehensive studies are needed to gain a better understanding of how the differences in formats impact on structural and functional characteristics. In this study, we designed and generated bispecific T-cell-engaging antibodies with IgG-like (DVD-Ig) and non-IgG (BiTE) formats. Both target the same pair of antigens (EGFR and CD3) to minimize the possible influence of targets on functional characterization. We performed a side-by-side comparison to assess differences in the physiochemical and biological properties of these two bispecific T-cell-engaging antibodies using a variety of breast and ovarian cancer cell-based functional assays to delineate the structural-functional relationships and anti-tumor activities/potency. We found that the Fc portion of T-cell-engaging bispecific antibodies can significantly impact antigen binding activity, potency, and stability in addition to eliciting different mechanisms of action that contribute the killing of cancer cells.

A comprehensive literature review and an international expert consensus on the management of scalp seborrheic dermatitis in adults.

Seborrheic Dermatitis of the scalp (SSD) is a chronic and relapsing inflammatory skin condition. Current SSD treatments mainly consist of topical applications of anti-fungals and anti-inflammatory agents. to review information about SSD and to provide dermatologists with practical recommendations for managing adult SSD. Material and methods: Between September and December 2023, an international group of experts in dermatology and hair and scalp disorders met to discuss published data about SD, SSD, dandruff, and management options. A total of 131 manuscripts available from PubMed were analysed, discussed and used for the present consensus. Each author was asked to complete a table listing currently used treatments to treat SSD according to the literature and to their own experience. The authors confirmed their use and regimen and commented on local treatment exceptions. They then agreed on prescription practices and proposed a general treatment approach. Currently, approved therapies to manage moderate and severe forms of SSD do not exist and there is a need for adapted and approved medications that treat efficiently and safely the disease. We propose a treatment algorithm that allows for the treatment of all severity grades of SSD. This algorithm may be completed with local treatment specifications. Despite the lack of approved therapies to manage moderate forms of SSD, a treatment algorithm is proposed and may help prescribers to manage SSD more efficiently.

A Platform for the Synthesis of Diverse Phosphonyl and Thiofunctionalized Sulfoxonium Ylides.

A practical strategy for the construction of diverse phosphonyl and thiofunctionalized sulfoxonium ylides via controllable monofunctionalization of hybrid I(III)/S(VI) ylides is presented. This process allows efficient P-H insertion of I(III)/S(VI) ylides under Cu catalysis, enabling the synthesis of phosphonyl sulfoxonium ylides, whereas reaction with sulfur-containing reagents including AgSCF3, KSC(S)OR, and KSCN under mild conditions resulted in α-trifluoromethylthiolation, dithiocarbanation, and thiocyanation of sulfoxonium ylides accordingly. Of note, wide substrate compatibility (108 examples), excellent efficiency (up to 99% yield), gram-scale experiments, and various product derivatizations highlight the synthetic utility of this protocol.