Thermodynamic determination of RNA duplex stability in magnesium solutions.

The prediction of RNA secondary structure and thermodynamics from sequence relies on free energy minimization and nearest neighbor parameters. Currently, algorithms used to make these predictions are based on parameters from optical melting studies performed in 1 M NaCl. However, many physiological and biochemical buffers containing RNA include much lower concentrations of monovalent cations and the presence of divalent cations. In order to improve these algorithms, thermodynamic data was previously collected for RNA duplexes in solutions containing 71, 121, 221, and 621 mM Na+. From this data, correction factors for free energy (ΔG°37) and melting temperature (Tm) were derived. Despite these newly derived correction factors for sodium, the stabilizing effects of magnesium have been ignored. Here, the same RNA duplexes were melted in solutions containing 0.5, 1.5, 3.0, and 10.0 mM Mg2+ in the absence of monovalent cations. Correction factors for Tm and ΔG°37 were derived to scale the current parameters to a range of magnesium concentrations. The Tm correction factor predicts the melting temperature within 1.2°C, and the ΔG°37 correction factor predicts the free energy within 0.30 kcalmol. These newly derived magnesium correction factors can be incorporated into algorithms that predict RNA secondary structure and stability from sequence.

The allelopathic, adhesive, hydrophobic and toxic latex of Euphorbia species is the cause of fairy circles investigated at several locations in Namibia.

BACKGROUND: In this multidisciplinary study we present soil chemical, phytochemical and GIS spatial patterning evidence that fairy circles studied in three separate locations of Namibia may be caused by Euphorbia species. RESULTS: We show that matrix sand coated with E. damarana latex resulted in faster water-infiltration rates. GC-MS analyses revealed that soil from fairy circles and from under decomposing E. damarana plants are very similar in phytochemistry. E. damarana and E. gummifera extracts have a detrimental effect on bacteria isolated from the rhizosphere of Stipagrostis uniplumis and inhibit grass seed germination. Several compounds previously identified with antimicrobial and phytotoxic activity were also identified in E. gummifera. GIS analyses showed that perimeter sizes and spatial characteristics (Voronoi tessellations, distance to nearest neighbour ratio, pair correlation function and L-function) of fairy circles are similar to those of fairy circles co-occurring with E. damarana (northern Namibia), and with E. gummifera (southern Namibia). Historical aerial imagery showed that in a population of 406 E. gummifera plants, 134 were replaced by fairy circles over a 50-year period. And finally, by integrating rainfall, altitude and landcover in a GIS-based site suitability model, we predict where fairy circles should occur. The model largely agreed with the distribution of three Euphorbia species and resulted in the discovery of new locations of fairy circles, in the far southeast of Namibia and part of the Kalahari Desert of South Africa. CONCLUSIONS: It is proposed that the allelopathic, adhesive, hydrophobic and toxic latex of E. damarana, E. gummifera, and possibly other species like E. gregaria, is the cause of the fairy circles of Namibia in the areas investigated and possibly in all other areas as well.

Selective Dorsal Rhizotomy For Treatment of Spasticity After Hemispherectomy In Children: A Case Report.

Performing a hemispherotomy or hemispherectomy is known to treat medically intractable epilepsy successfully, yet contralateral hemiparesis and increased muscle tone follow the epilepsy surgery. Spasticity and coexisting dystonia presumably cause the increased muscle tone in the lower extremity on the opposite side of epilepsy surgery. However, the extent of the role of spasticity and dystonia in high muscle tone is unknown. A selective dorsal rhizotomy is performed to reduce spasticity. If a selective dorsal rhizotomy is performed in the affected patient and muscle tone is reduced, the high muscle tone is not due to dystonia. Two children, who previously underwent a hemispherectomy or hemispherotomy, had a selective dorsal rhizotomy (SDR) performed in our clinic. Both children underwent orthopedic surgery to treat heel cord contractures. To study the extent of the role of spasticity and dystonia in high muscle tone, the mobility of the two children was examined pre- and post-SDR. The children had follow-ups 12 months and 56 months after SDR to study long-term effects. Before SDR, both children showed signs of spasticity. The SDR procedure removed spasticity, and muscle tone in the lower extremity became normal. Importantly, dystonia did not surface after SDR. Patients started independent walking less than two weeks after SDR. Sitting, standing, walking, and balance improved. They could walk longer distances while experiencing less fatigue. Running, jumping, and other more vigorous physical activities became possible. Notably, one child showed voluntary foot dorsiflexion that was absent before SDR. The other child showed improvement in voluntary foot dorsiflexion that was present before SDR. Both children maintained the progress at the 12 and 56-month follow-up visits. The SDR procedure normalized muscle tone and improved ambulation by removing spasticity. The high muscle tone following the epilepsy surgery was not due to dystonia.

Parent-Reported Outcomes of Early Childhood Selective Dorsal Rhizotomy for the Treatment of Spastic Diplegia.

Background A selective dorsal rhizotomy (SDR) is employed to treat spastic cerebral palsy. The surgical techniques and patient care protocols vary among hospitals. One of the variations is the age cut-off for SDR. We have been advocating SDR to be performed early - especially at ages 2 and 3. With this study, we are reporting the feasibility and parent-reported surgical outcomes of receiving SDR at an early age for the treatment of spastic diplegia. Objectives Our aim is to examine the safety and benefits of receiving SDR at the ages of 2 and 3 for the treatment of spastic diplegia. Methods The Institutional Review Board (IRB) of Washington University School of Medicine approved this retrospective quality of life survey and chart review (approval #202009056). The subjects of this study were children and teens (ages: 3.9-18.1) with spastic diplegic cerebral palsy who underwent SDR at ages 2 or 3 between years 2005 and 2019 at St. Louis Children's Hospital. Only domestic patients that were minors at the time of the study were selected to be participants in compliance with IRB regulations to protect patient health information that could potentially be breached by sending information to an incorrect or dated email. Thus, all contact was made through postal mail. The study included 141 patients from a total of 362 eligible patients. Parents of eligible patients were sent the research survey via postal mail. Only patients who responded to the survey were included in this study. The survey included questions on demographic information, quality of life, health perception, motor and ambulatory functions, braces and orthotics, pain issues, side effects of SDR, and post-SDR treatment. Results The study included 141 diplegic patients. Of all patients at the time of the study, 91% reported an improvement in walking, 92% in standing, and 89% in sitting. In daily life activities, 87% of patients became more independent after SDR. 65% of patients were able to walk without a walking aid and about 4% were not able to walk. 11% of all patients relied mostly on a wheelchair. Moreover, 43% of patients were able to run independently. Regarding post-SDR orthopedic surgery, 48% of patients received at least one type of orthopedic surgery, with Achilles tendon lengthening, hamstring lengthening, and calf muscle release being the most common types.  Conclusions SDR performed at an early age through a single-level laminectomy was proved feasible and safe. A follow-up until the adult age (18 years) showed improvements in walking and other motor functions. The results support the implementation of early-age SDR for the treatment of spastic diplegia.

Selective Dorsal Rhizotomy for Treatment of Hereditary Spastic Paraplegia-Associated Spasticity in 37 Patients.

Background A limited number of publications have described a reduction of spasticity associated with hereditary spastic paraplegia (HSP) after selective dorsal rhizotomy (SDR). Typically, the SDR procedure is performed on patients with spastic cerebral palsy to remove spasticity and to help these patients with ambulatory function. Whether SDR has similar effects on HSP patients, requires further investigation. Thus, we are providing a personal experience of the effects of SDR on this specific cohort of patients. Objectives To examine the safety of SDR, changes in spasticity, and ambulatory function after SDR on patients with HSP. Methods The Institutional Review Board of Washington University School of Medicine approved this study (#201704003). A total of 37 children and adults received SDR for the treatment of HSP-associated spasticity between 1988 and 2021. SDR was performed through an L1 laminectomy, as we previously described in an earlier publication. The patients took part in the follow-up examination either in-person or by email. The follow-up focused on the patients' motor functions (primarily ambulation), adverse effects of SDR, and orthopedic treatments after SDR. Results Of the total 37 patients who participated in this study, 46% were female and 54% were male. The age range of when HSP was diagnosed was one month to 34 years. Six of the patients' diagnoses were made, based on the family history of HSP in six patients and the remaining 31 patients' diagnoses were confirmed by genetic tests. The most common genetic mutations were SPG4 and SPG3A. Of the patients with positive genetic tests, 40% had no family history of HSP. SDR was performed at the age of 2 to 45 years (mean: 14.7 years). The follow-up period ranged from 0 to 33 years (mean: 3.8 years). One patient developed a spinal fluid leak requiring surgical repair. Two patients reported mild numbness in parts of the lower limbs. Spasticity was removed in 33 patients (89%). Four patients (11%) experienced a return in spasticity. Regarding ambulatory function, 11% of patients reported a decline in function. Two patients walked independently before surgery but declined, requiring a wheelchair eight years and seven years, respectively, after surgery for each patient. In contrast, 16% saw an improvement in ambulatory function, improving from walking with a walker to walking independently. The remaining 73% of patients maintained their level of ambulation. These two groups of patients showed improvement in other motor functions and independence.  Conclusions The present analysis suggests the potential role of SDR in the management of spasticity in HSP patients. We found no sign of SDR being a direct cause of deleterious effects on patients with HSP.

Selective Dorsal Rhizotomy for the Treatment of Spastic Hemiplegic Cerebral Palsy.

Background Selective dorsal rhizotomy (SDR) can remove spasticity in cerebral palsy (CP). Spastic hemiplegia is associated with spasticity in the upper and lower limbs on one side. Only a single report described the outcome of SDR specifically in patients with spastic hemiplegic CP. The effect of SDR on spastic hemiplegia requires further investigation. Objectives To analyze the outcomes of motor functions, the quality of life, and satisfaction of patients who received SDR for the treatment of spastic hemiplegia. Methods A total of 29 children and 1 adult who received SDR were surveyed. The survey questionnaire asked about demographic information, patient's perception of SDR, functional outcomes, SDR surgical outcomes, pain, braces/orthotics, and post-SDR treatment. Results Our study included 30 patients. The age at the time of surgery was 2 to 36 years. The follow-up period ranged from one to six years. Of all parents, 90% of parents reported that SDR benefited their children, and 93% stated that they would recommend the SDR procedure to other families of children with hemiplegic CP. Of all patients, 90% reported improved walking, 63% reported improved sitting, and 87% reported improved balance and posture. In daily life functioning after the SDR, 67% were more independent and confident. Moreover, 33% of patients were pain-free and 43% had reduced pain in their legs and back. In activities of daily living, 93% transferred independently from one position to another. A majority of the patients reported regular strengthening and stretching of the lower limb, and 50% of the patients played sports. A majority (73%) of patients underwent post-SDR orthopedic surgery for heel cord, hamstring, and adductor contractures. Five patients experienced numbness in the small part of the lower limb after SDR. None reported that the numbness affected their daily activities. One child required surgical repair of the cerebrospinal fluid leak. Conclusions In our 29 children and 1 adult with spastic hemiplegia, SDR improved motor function and daily life function. Nearly all parents of children and the one adult felt that SDR was beneficial and that they would recommend surgery to other children with spastic hemiplegia.

Functional Outcome of Adulthood Selective Dorsal Rhizotomy for Spastic Diplegia.

Objective The medical evidence supporting the efficacy of selective dorsal rhizotomy (SDR) on children with spastic diplegia is strong. However, the outcome of SDR on adults with spastic diplegia remains undetermined. The aim is to study the effectiveness and morbidities of SDR performed on adults for the treatment of spastic diplegia.  Methods Patients who received SDR in adulthood for the treatment of spastic diplegia were surveyed. The survey questionnaire addressed the living situation, education level, employment, health outcomes, postoperative changes of symptoms, changes in ambulatory function, adverse effects of SDR and orthopedic surgery after SDR.  Results The study included 64 adults, who received SDR for spastic diplegia. The age at the time of surgery was between 18 and 50 years. The age at the time of the survey was between 20 and 52 years. The follow-up period ranged from one to 28 years. The study participants reported post-SDR improvements of the quality of walking in 91%, standing in 81%, sitting in 57%, balance while walking 75%, ability to exercise in 88%, endurance in 77%, and recreational sports in 43%. Muscle and joint pain present before surgery improved in 64% after surgery. Concerning the level of ambulatory function, all patients who walked independently in all environments maintained the same level of ambulatory function. Eighteen percent of the patients who walked independently in some environments improved to the independent walking in all environments. All patients who walked with an assistive device before SDR maintained the assistive walking after SDR. Concerning adverse effects of SDR, 50% (32 of 64 patients) developed numbness in the various parts of the legs. Two patients reported a complete loss of sensation in parts of the legs, and one patient reported numbness and constant pain in the bilateral lower extremities. Ten patients (16%) reported recurrent spasticity after SDR, and three patients (5%) reported ankle clonus, which is an objective sign of spasticity. Tendon lengthening surgery after SDR was needed in 27% and hip and knee surgery in 2% and 6%, respectively.  Conclusions The great majority of our 64 patients, who received adulthood SDR for spastic diplegia, improved the quality of ambulation and abated signs of early aging. Numbness and diminished sensation in the lower extremity was the most common adverse effect of the adulthood SDR.