Extreme Fuzzy Broad Learning System: Algorithm, Frequency Principle, and Applications in Classification and Regression.

As an effective alternative to deep neural networks, broad learning system (BLS) has attracted more attention due to its efficient and outstanding performance and shorter training process in classification and regression tasks. Nevertheless, the performance of BLS will not continue to increase, but even decrease, as the number of nodes reaches the saturation point and continues to increase. In addition, the previous research on neural networks usually ignored the reason for the good generalization of neural networks. To solve these problems, this article first proposes the Extreme Fuzzy BLS (E-FBLS), a novel cascaded fuzzy BLS, in which multiple fuzzy BLS blocks are grouped or cascaded together. Moreover, the original data is input to each FBLS block rather than the previous blocks. In addition, we use residual learning to illustrate the effectiveness of E-FBLS. From the frequency domain perspective, we also discover the existence of the frequency principle in E-FBLS, which can provide good interpretability for the generalization of the neural network. Experimental results on classical classification and regression datasets show that the accuracy of the proposed E-FBLS is superior to traditional BLS in handling classification and regression tasks. The accuracy improves when the number of blocks increases to some extent. Moreover, we verify the frequency principle of E-FBLS that E-FBLS can obtain the low-frequency components quickly, while the high-frequency components are gradually adjusted as the number of FBLS blocks increases.

Mesoporous Iron Family Element (Fe, Co, Ni) Molybdenum Disulfide/Carbon Nanohybrids for High-Performance Supercapacitors.

As the demand for fuel continues to increase, the development of energy devices with excellent performance is crucial. Supercapacitors (SCs) are attracting attention for their advantages of high specific energy and a long cycle life. At present, the development of high-performance electrode materials is the main point for research and development of SCs. Transition metal sulfides have the advantages of a large interlayer space and high theoretical capacity, making them promising electrode materials. Herein, we reported a series of ultrathin mesoporous iron family element (Fe, Co, Ni) molybdenum disulfide (MxMo1-xS2/C, M = Fe, Co, and Ni) by a template method. The original monolayer mesoporous structure of MoS2/C was maintained, and accumulation and agglomeration of MoS2/C were avoided. Based on our investigations, the best performance was that of CoxMo1-xS2/C nanohybrids. Furthermore, the concentrations of Co and Mo ions were modulated to obtain the best performance, in which Mo and Co ions were released at 1:1, 1:2, and 1:3 ratios and they were named CoxMo1-xS2/C-1, CoxMo1-xS2/C-2, and CoxMo1-xS2/C-3, respectively. Overall, these materials represent a significant improvement and show promise as high-performance SC electrode materials due to their enhanced capacitance and stability. At a current density of 0.5 A g-1, CoxMo1-xS2/C-2 has the optimal specific capacitance of 184 F g-1. CoxMo1-xS2/C-2 as an SC electrode exhibited better reversible capacity and cycling stability than MoS2/C, which is an improvement over MoS2/C regarding reversible capacity and cycling stability.

Freestanding narrowband terahertz filters based on aluminum foil.

Terahertz (THz) filters with high transmission coefficient (T) in the passband and frequency selectivity are critical in numerous applications such as astronomical detection and next-generation wireless communication. Freestanding bandpass filters eliminate the Fabry-Pérot effect of substrate, thus providing a promising choice for cascaded THz metasurfaces. However, the freestanding bandpass filters (BPFs) using the traditional fabrication process are costly and fragile. Here, we demonstrate a methodology to fabricate THz BPFs using aluminum (Al) foils. We designed a series of filters with center frequencies below 2 THz and manufacture them on 2-inch Al foils with various thicknesses. By optimizing the geometry, T of the filter at the center frequency is over 92%, and the relative full-width half maxima (FWHM) is as narrow as 9%. The responses of BPFs show that "cross-shaped" structures are insensitive to the polarization direction. The simple and low-cost fabrication process of the freestanding BPFs promise their widespread applications in THz systems.

Doxycycline Promotes Graft Healing and Attenuates Posttraumatic Osteoarthritis After Anterior Cruciate Ligament Reconstruction in a Rat Model.

BACKGROUND: Doxycycline (Doxy) has been shown to facilitate tendon healing by reducing on-site matrix metalloproteinase (MMP) activity, but its effect on graft healing after anterior cruciate ligament reconstruction (ACLR) has not been investigated, and the therapeutic effect of Doxy in preventing ACLR-induced posttraumatic osteoarthritis (PTOA) is unclear. HYPOTHESIS: Doxy promotes graft healing and alleviates the progression of PTOA after ACLR. STUDY DESIGN: Controlled laboratory study. METHODS: Sprague Dawley rats (n = 74; age, 12-13 weeks; male) that underwent ACLR were divided into untreated control and Doxy treatment (50 mg/kg/d orally until sacrifice) groups. At 2 and 6 weeks after surgery, graft healing was assessed by biomechanical testing, histology, immunohistochemical staining, and micro-computed tomography (µCT). The progression of PTOA was evaluated at 6 weeks by histology, the Mankin score, and immunofluorescence staining of the tibial plateau, and osteophyte formation was evaluated by µCT. Hindlimb weight distribution was evaluated at 6 weeks, and gait patterns were evaluated at 2 and 6 weeks. Intra-articular MMP activity was evaluated at 6 weeks in vivo using an MMP-activatable near-infrared fluorescent probe. RESULTS: Graft healing was enhanced by Doxy treatment, and the ultimate failure load (P = .002) and stiffness of the graft (P = .007) were significantly higher in the Doxy group at week 2. Bone mineral density and bone volume/total volume for both the tibial and the femoral tunnels at week 6 in the Doxy group were significantly higher compared with in the control group (P < .05). The overall graft healing scores were significantly higher in the Doxy group. Doxy treatment enhanced graft integration, intratunnel graft integrity, and collagen birefringence; more collagen types 1 and 10 and less MMP-13 were found at the graft-bone interface. At week 6, the Doxy group had a lower modified Mankin score (P = .033) and showed fewer MMP 13-positive chondrocytes at the articular cartilage surface (P = .002), indicating moderate joint cartilage damage. µCT revealed less osteophyte formation, and gait analysis revealed more symmetric weightbearing and gait patterns, after Doxy treatment at week 6 (P < .05). In vivo imaging with the near-infrared fluorescent probe identified significantly lower intra-articular MMP activity in the Doxy group at week 6 (P = .016). CONCLUSION: The oral administration of Doxy was able to synchronously promote graft healing and attenuate PTOA in an ACLR rat model. CLINICAL RELEVANCE: Our results indicated that Doxy, a widely used drug, is potentially beneficial to patients after ACLR.

Bioactive Decellularized Tendon-Derived Stem Cell Sheet for Promoting Graft Healing After Anterior Cruciate Ligament Reconstruction.

BACKGROUND: Stem cell sheets provide a scaffold-free option for the promotion of graft healing after anterior cruciate ligament reconstruction (ACLR). However, cell viability, stability, and potential uncontrolled actions create challenges for clinical translation. The decellularization of cell sheets may overcome these problems as studies have shown that the natural extracellular matrix of stem cells is bioactive and can promote tissue repair. HYPOTHESIS: The decellularized tendon-derived stem cell (dTDSC) sheet can promote graft healing after ACLR. STUDY DESIGN: Controlled laboratory study. METHODS: An optimized decellularization protocol was developed to decellularize the TDSC sheets. A total of 64 Sprague-Dawley rats underwent ACLR with or without the dTDSC sheet wrapping the tendon graft (n = 32/group). At 2 and 6 weeks after surgery, graft healing was assessed by micro-computed tomography, histology, and biomechanical testing. The accumulation of iNOS+ and CD206+ cells and the expression of metalloproteinase 1 (MMP-1), MMP-13, and tissue inhibitor of metalloprotease 1 (TIMP-1) were assessed by immunohistochemistry. RESULTS: The decellularization was successful, with the removal of 98.4% nucleic acid while preserving the collagenous proteins and bioactive factors. The expression of bone morphogenetic protein 2 (BMP-2) and VEGF in the dTDSC sheet was comparable with the TDSC sheet (P > .05). Micro-computed tomography showed significantly more tunnel bone formation in the dTDSC sheet group. The dTDSC sheet group demonstrated better graft osteointegration and higher integrity of graft midsubstance with significantly higher ultimate failure load (16.58 ± 7.24 vs 8.93 ± 2.45 N; P = .002) and stiffness (11.97 ± 5.21 vs 6.73 ± 2.20 N/mm; P = .027). Significantly fewer iNOS+ cells but more CD206+ cells, as well as lower MMP-1 and MMP-13 but higher TIMP-1 expression, were detected at the tendon-bone interface and graft midsubstance in the dTDSC sheet group. CONCLUSION: An optimized decellularization protocol for producing bioactive dTDSC sheets was developed. Wrapping tendon graft with a dTDSC sheet promoted graft healing after ACLR, likely via enhancing bone formation and angiogenesis by BMP-2 and VEGF, modulating macrophage polarization and MMP/TIMP expression, and physically protecting the tendon graft. CLINICAL RELEVANCE: dTDSC sheets alleviate the quality control and safety concerns of cell transplantation and can be used as a cell-free alternative for the promotion of graft healing in ACLR.

Application of suture anchors for a clinically relevant rat model of rotator cuff tear.

Current rat model of rotator cuff (RC) tear could not mimic the suture anchor (SA) repair technique in the clinical practice. We designed a novel SA for RC repair of rats to establish a clinically relevant animal model. Small suture anchors that fit the rat shoulder were assembled. 60 rats were assigned to the transosseous (TO) repair group or SA repair group (n = 30/group). Micro-computed tomography (Micro-CT) scanning, biomechanical test and histological analysis were implemented at 2, 4, and 8-week post-repair. The failure load and stiffness in the SA group were significantly higher than those of TO group at 4-week post-repair. Micro-computed tomography analysis showed the bone mineral density and trabecular thickness of the SA group were significantly lower than those of TO group. The SA group showed a better insertion continuity at 4-week post-repair compared to TO group. No significant difference in gait parameters was found between groups. Therefore, SA repair is applicable for the rat model of RC tears. The SA repair achieved superior RC tendon healing, but more extensive initial bone damage compared to TO repair, while the shoulder function was comparable. This model could replicate the current repair technique in the clinical situation and be considered for future preclinical studies on healing enhancement for RC tears. Statement of Clinical Significance: With high clinical relevance, this model may facilitate the translation from an animal study into clinical trials.

Roles of Oxidative Stress in Acute Tendon Injury and Degenerative Tendinopathy-A Target for Intervention.

Both acute and chronic tendon injuries are disabling sports medicine problems with no effective treatment at present. Sustained oxidative stress has been suggested as the major factor contributing to fibrosis and adhesion after acute tendon injury as well as pathological changes of degenerative tendinopathy. Numerous in vitro and in vivo studies have shown that the inhibition of oxidative stress can promote the tenogenic differentiation of tendon stem/progenitor cells, reduce tissue fibrosis and augment tendon repair. This review aims to systematically review the literature and summarize the clinical and pre-clinical evidence about the potential relationship of oxidative stress and tendon disorders. The literature in PubMed was searched using appropriate keywords. A total of 81 original pre-clinical and clinical articles directly related to the effects of oxidative stress and the activators or inhibitors of oxidative stress on the tendon were reviewed and included in this review article. The potential sources and mechanisms of oxidative stress in these debilitating tendon disorders is summarized. The anti-oxidative therapies that have been examined in the clinical and pre-clinical settings to reduce tendon fibrosis and adhesion or promote healing in tendinopathy are reviewed. The future research direction is also discussed.

Effect of a community-based child health counselling intervention on health-seeking behaviours, complementary feeding and nutritional condition among children aged 6-23 months in rural China: A pre- and post-comparison study.

In China, the prevalence of undernutrition among children under 5 years of age has declined significantly during recent decades. However, noticeable gaps exist between rural and urban areas. Since 2012, a government-funded nutrition programme, Ying Yang Bao (YYB; soybean powder-based iron-rich supplement) programme, has been implemented in poor rural areas to decrease the risk of developing anaemia among children aged 6-23 months, but there are still inadequate health care awareness, feeding knowledge and skills among caregivers. From June 2018 to December 2020, a child health counselling intervention was delivered through a home visit based on the YYB programme in Liangshan. Child health messages were given by trained village child health assistants while distributing YYB. Surveys were conducted before and after the intervention to analyse changes in child health check-up frequency, complementary feeding practice and prevalence of undernutrition. After the intervention, the proportion of children who had regular health check-ups, who were vaccinated and who met the minimum YYB consumption significantly increased from 26.0%, 81.6%, and 67.8% to 59.7%, 95.0%, and 79.2%. Increased rates of IYCF indicators (introduction of solid, semisolid, or soft foods, minimum dietary diversity and consumption of iron-rich or iron-fortified foods) were observed after the intervention. The prevalence of stunting, underweight, wasting, and anaemia significantly decreased from 26.3% to 10.8%, 13.4% to 8.7%, 14.0% to 10.5%, and 52.1% to 43.9%. This intervention can be well integrated into the YYB programme with less additional resources. Children in resource-limited areas will benefit more from a comprehensive nutritional package, including food supplements and child health education.

Graft healing after anterior cruciate ligament reconstruction (ACLR).

Anterior cruciate ligament reconstruction (ACLR) is a commonly performed procedure in Orthopaedic sports medicine. With advances in surgical techniques providing better positioning and fixation of the graft, subsequent graft failure to certain extent should be accounted by poor graft healing. Although different biological modulations for enhancement of graft healing have been tried in different clinical and animal studies, complete graft incorporation into bone tunnels and the "ligamentization" of the intra-articular part have not been fully achieved yet. Based on the understanding of graft healing process and its failure mechanism, the purpose of this review is to combine both the known basic science & clinical evidence, to provide a much clearer picture of the obstacle encountered in graft healing, so as to facilitate researchers on subsequent work on the enhancement of ACL graft healing.

A radial 3D polycaprolactone nanofiber scaffold modified by biomineralization and silk fibroin coating promote bone regeneration in vivo.

The treatment and repair of large bone defects remains a major therapeutic challenge in the clinical setting. Nanofiber scaffolds fabricated via the electrospinning technique have been developed as a universal method for bone regeneration due to their suitable properties. However, traditional two-dimensional (2D) nanofiber mats are usually too dense, which may prevent cell infiltration and growth, thereby restricting their application. Herein, a three-dimensional (3D) polycaprolactone nanofiber scaffold was developed, modified by biomineralization and silk fibroin coating. The scaffold possessed a parallel array of nanofiber surfaces, mimicking the parallel structure of fibrils in natural bone tissue. Furthermore, the fabricated radially or laterally interconnected macrochannels were investigated to elucidate the effect of the scaffold structure on bone regeneration. In vitro studies revealed that the scaffolds could guide cell arrangement and that the radially aligned scaffold demonstrated a stronger ability to promote cell proliferation. In vivo results showed that the radially aligned scaffold could guide tissue arrangement and remodeling and support a significantly faster regeneration rate of bone tissue. Therefore, 3D-mineralized polycaprolactone nanofiber scaffolds with radially interconnected macrochannels and aligned nanofibers are expected to be used in tissue engineering, including in the repair of bone defects, cartilage or other composite tissues.

Tackling the Challenges of Graft Healing After Anterior Cruciate Ligament Reconstruction-Thinking From the Endpoint.

Anterior cruciate ligament (ACL) tear is common in sports and accidents, and accounts for over 50% of all knee injuries. ACL reconstruction (ACLR) is commonly indicated to restore the knee stability, prevent anterior-posterior translation, and reduce the risk of developing post-traumatic osteoarthritis. However, the outcome of biological graft healing is not satisfactory with graft failure after ACLR. Tendon graft-to-bone tunnel healing and graft mid-substance remodeling are two key challenges of biological graft healing after ACLR. Mounting evidence supports excessive inflammation due to ACL injury and ACLR, and tendon graft-to-bone tunnel motion negatively influences these two key processes. To tackle the problem of biological graft healing, we believe that an inductive approach should be adopted, starting from the endpoint that we expected after ACLR, even though the results may not be achievable at present, followed by developing clinically practical strategies to achieve this ultimate goal. We believe that mineralization of tunnel graft and ligamentization of graft mid-substance to restore the ultrastructure and anatomy of the original ACL are the ultimate targets of ACLR. Hence, strategies that are osteoinductive, angiogenic, or anti-inflammatory should drive graft healing toward the targets. This paper reviews pre-clinical and clinical literature supporting this claim and the role of inflammation in negatively influencing graft healing. The practical considerations when developing a biological therapy to promote ACLR for future clinical translation are also discussed.

Effects of baby-friendly practices on breastfeeding duration in China: a case-control study.

BACKGROUND: The Baby-Friendly Hospital Initiative is generally considered an effective way to promote breastfeeding. Although China has the largest number of baby-friendly hospitals in the world, research on baby-friendly practices in China is limited, and the rate of exclusive breastfeeding (EBF) at 6 months, 20.7%, compared to the 2025 global goal of 50% is low. It is, therefore, important to determine the factors that remain significant barriers to EBF in China. To explore how the key baby-friendly practices affect EBF duration in China, we used a case-control study to compare the effects of baby-friendly-related practices on both EBF and non-breastfeeding (NBF) mothers at 3 months and to investigate the effects of both single and comprehensive baby-friendly practices in promoting EBF duration at 3 months, which is one step toward EBF at 6 months. METHODS: Participants were recruited from four maternal and child health hospitals in western (Chongqing), eastern (Qingdao), southern (Liuzhou), and central China (Maanshan). A total of 421 mothers (245 in the EBF group, 176 in the NBF group) of infants aged 3 months were surveyed through a self-reported questionnaire from April 2018 to March 2019. The experience of baby-friendly practices and breastfeeding during hospitalization were assessed with yes/no questions. Socio-demographic factors that influenced breastfeeding at 3 months were analyzed using bivariate and multivariate logistic regression analyses. RESULTS: Of mothers in the EBF group, 65.57% reported engaging in at least seven baby-friendly practices compared to 47.72% of mothers in the NBF group. Significantly more mothers in the EBF group engaged in baby-friendly practices than in the NBF group. These practices included "breastfeeding within one hour after birth" (74.29% vs. 59.09%), "breastfeeding on demand" (86.48% vs. 75.00%), and "never use a pacifier" (46.53% vs. 31.25%). After adjusting for confounding variables, we found that the mothers who engaged in fewer than seven baby-friendly practices were about 1.7 times less likely to breastfeed than were those who engaged in seven or more baby-friendly practices (odds ratio [OR] 1.720, 95% confidence interval [CI] 1.106, 2.667). Further, the mothers who did not breastfeed on demand were as likely to not breastfeed up to 3 months (OR 2.263, 95% CI 1.265, 4.049), as were mothers who did not breastfeed during hospitalization (OR 4.379, 95% CI 1.815, 10.563). CONCLUSIONS: These data from hospitals in China suggest that higher compliance with baby-friendly practices may have a positive impact on EBF at 3 months, particularly in terms of promoting the implementation of breastfeeding on demand and breastfeeding during hospitalization in China.

Inadequate Nutrition and Associated Factors in Children Aged 6 to 24 Months - 4 Counties, Liangshan Yi Autonomous Prefecture, China, 2018.

What is already known about this topic? Symptoms of malnutrition including anemia, stunting, wasting, and being underweight among children remained one of the major public health problems in poorer areas in China. More research is needed to guide interventions to improve nutrition and health among children in low-income regions. What is added by this report? The prevalences of anemia, stunting, wasting, and being underweight were 51.9%, 25.6%, 14.6%, and 9.5%, respectively, among children aged 6 to 24 months in the poorest areas of Liangshan. Associated factors were gender, age, education level and occupation of mother, breastfeeding, and caregiver knowledge. What are the implications for public health practice? Improving caregiver knowledge of nutrition and child feeding practices is crucial to address malnutrition among children. These findings can help more precisely understand the child health needs in poorer areas in order to develop effective interventions. They also provide evidence-based information to formulate child health promotion strategies in other countries with similar situations.

Overexpression of miR-335 inhibits the migration and invasion of osteosarcoma by targeting SNIP1.

MicroRNAs (miRNAs) are key regulators in the development and progression of osteosarcoma (OS). Based on our previous microarray data, we found that miR-335 expression was downregulated in OS tissue relative to normal tissue. Herein, we further found that miR-335 was downregulated in OS cell lines relative to the osteoblastic cell line hFOB 1.19. Further functional experiments found that upregulation of miR-335 suppressed the proliferation, invasion and migration of OS cells in vitro and tumor growth and lung metastasis in vivo. In addition, the expression of a total of 750 mRNAs was decreased upon the upregulation of miR-335, and SNIP1 was found to be the direct target of miR-335. Restoration of SNIP1 expression attenuated the suppressive effect of miR-335 on OS cells. Additionally, miR-335 suppressed the mRNA and protein expression of SNIP1, MMP-2, and MMP-7 in vitro and in vivo. MiR-335 also suppressed c-Myc and NFκb p65 in vitro and in vivo. In conclusion, our data suggest that miR-335 plays a significant role in the tumorigenesis and metastasis of OS and may serve as a therapeutic target for OS treatment.

Porous and nonporous silk fibroin (SF) membranes wrapping for Achilles tendon (AT) repair: Which one is a better choice?

Two types of silk fibroin (SF) membranes were developed for tendon repair: porous and nonporous SF membranes. The objective of this study was to compare the efficiency of these two films according to the ability of tendon regeneration using a rat Achilles tendon (AT) rupture suture wrapping model. The in vitro tests were conducted, and theSF membranes were proved to be with ultimate-biodegradability, good-biocompatibility and without toxicity. In vivo, 12 Sprague Dawley rats were used to create a rat AT rupture suture model wrapped by SF membranes. They were randomly divided into six groups. The results revealed that the nonporous SF membrane wrapping group was shown to reduce the inflammatory effect and induce the proliferation of fibroblast-like cells at one week and four weeks post-operatively. After four weeks, the nonporous SF membrane wrapping group exhibited more organized collagen structures and had increased expression of tendon repair proteins. Hence, our nonporous SF membrane improved the efficacy of tendon regeneration by decreasing inflammatory cells, growing fibroblast-like cells, and promoting extracellular matrix production. Nonporous SF membrane can, therefore, be regarded as a better functional membrane for tendon repair. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: 00B: 000-000, 2018. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 733-740, 2019.

A novel subchondral bone-grafting procedure for the treatment of giant-cell tumor around the knee: A retrospective study of 27 cases.

The vast majority of giant-cell tumors occur around the knee and characteristically affect the subchondral bone. Thermal damage to the articular cartilage arising from the application of polymethylmethacrylate (PMMA) or extensive intralesional curettage presents a challenging problem to orthopedic surgeons and patients due to compliance issues. For this reason, we developed a new subchondral bone-grafting procedure to restore massive bone defects and reduce degenerative changes in the knee.The aim of this study was to describe the novel subchondral bone-grafting procedure and evaluate clinical outcomes in patients with giant-cell tumors around the knee.This retrospective single-center study included a total of 27 patients with giant-cell tumors in the distal femur and proximal tibia admitted to our department from January 2012 to December 2015 and treated with aggressive intralesional curettage. Eleven males and 16 females were included. All cases underwent subchondral autograft bone grafting followed by bone cement reconstruction and instrument internal fixation. The Musculoskeletal Tumor Society (MSTS) score and short form-36 (SF-36) were applied to assess the functional outcome of the knee joint and quality of life. Tumor recurrence, Kellgren and Lawrence (KL) grade, and the distance of the cement to the articular surface were assessed throughout the sample.All cases were followed up after surgery for an average of 32.9 ±â€Š7.1 months (range 25-57 months). At the end of the follow-up period, all patients were alive and free from pulmonary metastasis. Complications associated with this surgery occurred only in 1 patient (3.7%), who presented with an incision infection that resolved with regular dressing and antibiotics. No fractures, instrument breakage, or joint fluid leakage occurred. Local recurrence occurred in 1 case (3.7%) at the distal femur after 23 months and was treated by wide resection followed by prosthesis reconstruction. Twenty-four patients (89%) did not develop radiographic findings of osteoarthritis: at the final follow-up 2 patients (7.4%), had progressed to KL1 and 1 patient had progressed to KL2. According to the MSTS scoring system, the functional score of the affected knee joint at the last follow-up ranged from 80% to 97%, with an average of 87.3%. The quality of life parameters assessed by the SF-36 survey at the last follow-up ranged from 47 to 96, with an average of 77.For patients with giant-cell tumor of bone near the knee, subchondral bone grafting combined with bone cement reconstruction is recommended as a feasible and effective treatment modality.

An RNA pyrophosphohydrolase triggers 5'-exonucleolytic degradation of mRNA in Bacillus subtilis.

In Escherichia coli, RNA degradation often begins with conversion of the 5'-terminal triphosphate to a monophosphate, creating a better substrate for internal cleavage by RNase E. Remarkably, no homolog of this key endonuclease is present in many bacterial species, such as Bacillus subtilis and various pathogens. Here, we report that the degradation of primary transcripts in B. subtilis can nevertheless be triggered by an analogous process to generate a short-lived, monophosphorylated intermediate. Like its E. coli counterpart, the B. subtilis RNA pyrophosphohydrolase that catalyzes this event is a Nudix protein that prefers unpaired 5' ends. However, in B. subtilis, this modification exposes transcripts to rapid 5' exonucleolytic degradation by RNase J, which is absent in E. coli but present in most bacteria lacking RNase E. This pathway, which closely resembles the mechanism by which deadenylated mRNA is degraded in eukaryotic cells, explains the stabilizing influence of 5'-terminal stem-loops in such bacteria.

Decay of a model mRNA in Bacillus subtilis by a combination of RNase J1 5' exonuclease and RNase Y endonuclease activities.

The involvement of the recently characterized 5' exonuclease activity of RNase J1 and endonuclease activity of RNase Y in the turnover of ΔermC mRNA in Bacillus subtilis was investigated. Evidence is presented that both of these activities determine the half-life of ΔermC mRNA.

Successful treatment of central pain in a multiple sclerosis patient with epidural stimulation of the dorsal root entry zone.

OBJECTIVE: We report a case of central pain successfully treated by epidural placement of spinal cord stimulator electrodes. Neuromodulation of primary afferent fibers and the underlying dorsal root entry zone provided effective analgesia whereas traditional lead placement over the dorsal columns on a prior occasion had not been effective. The rationale for this technique based on current understanding of the mechanisms of central pain and the risk/benefit considerations are discussed. CASE REPORT: A 52-year-old woman presented with a 2-year history of pain in the lateral hand secondary to a demyelinating episode in the C2-4 spinal cord secondary to multiple sclerosis. Medications, sympathetic blocks, and acupuncture had been ineffective. One year after an unsuccessful single-lead trial of spinal cord stimulation over the cervical dorsal columns, a dual-lead trial of spinal cord stimulation over the lateral cervical spinal cord and dorsal roots provided significant analgesia, prompting a successful permanent implant. OUTCOME MEASURES: Responses on the Brief Pain Inventory short form and quantitative thermosensory testing data were collected at two timepoints 16 days apart under two conditions: no stimulation and single-lead stimulation of cervical primary afferents and underlying spinal cord. RESULTS: The patient's questionnaire responses indicated significantly improved pain scores with lateral-lead neuromodulation that was associated with a reduction in her baseline heat hypoalgesia. CONCLUSIONS: Lateral-lead spinal cord stimulation may be effective for some central pain syndromes through a partial restoration of homeostatic small-fiber signaling. Neuroanatomical and physiological data in a larger population of patients will be required to predict the best responders to this therapeutic modality.

Initiation of decay of Bacillus subtilis rpsO mRNA by endoribonuclease RNase Y.

rpsO mRNA, a small monocistronic mRNA that encodes ribosomal protein S15, was used to study aspects of mRNA decay initiation in Bacillus subtilis. Decay of rpsO mRNA in a panel of 3'-to-5' exoribonuclease mutants was analyzed using a 5'-proximal oligonucleotide probe and a series of oligonucleotide probes that were complementary to overlapping sequences starting at the 3' end. The results provided strong evidence that endonuclease cleavage in the body of the message, rather than degradation from the native 3' end, is the rate-determining step for mRNA decay. Subsequent to endonuclease cleavage, the upstream products were degraded by polynucleotide phosphorylase (PNPase), and the downstream products were degraded by the 5' exonuclease activity of RNase J1. The rpsO mRNA half-life was unchanged in a strain that had decreased RNase J1 activity and no RNase J2 activity, but it was 2.3-fold higher in a strain with decreased activity of RNase Y, a recently discovered RNase of B. subtilis encoded by the ymdA gene. Accumulation of full-length rpsO mRNA and its decay intermediates was analyzed using a construct in which the rpsO transcription unit was under control of a bacitracin-inducible promoter. The results were consistent with RNase Y-mediated initiation of decay. This is the first report of a specific mRNA whose stability is determined by RNase Y.