Case Series: Intrathecal Baclofen Therapy in Stiff-Person Syndrome.

OBJECTIVES: Stiff-person syndrome (SPS) is associated with axial rigidity superimposed on sustained muscle spasms. These symptoms commonly interfere with the performance of activities of daily living including ambulation. This retrospective case series evaluates the outcomes of screening tests and chronic infusion of intrathecal baclofen (ITB) in patients diagnosed with SPS treated in our spasticity clinic. MATERIALS AND METHODS: Patients were identified from an institutional review board-approved clinical registry of ITB therapy. Data from clinical encounters were extracted from the registry and from the patients' electronic medical record. All patients with medically refractory spasticity related to SPS screened with an ITB injection were included. In addition to pertinent demographic and clinical information, data from validated outcome measures routinely used in the clinic were collected: pain Numeric Rating Scale, Spasm Frequency Scale, lower extremity Modified Ashworth Scale (MAS), and Timed 25 Foot Walk. Outcomes data for chronic ITB infusion were assessed at early (<6 months) and late follow-up (6-12 months) visits after surgery. RESULTS: Nine patients were included, and seven received chronic ITB infusion. MAS scores were improved at early and late follow-up, and five patients experienced a reduction in pain scores. Walking performance remained stable in previously ambulatory patients. Four patients experienced complications related to ITB implantation, which resolved with medical or surgical treatment. CONCLUSION: Consistent with other case series, our results suggest that ITB is an effective therapy for medically intractable spasticity due to SPS, and symptom reduction can be achieved without compromising ambulation.

Exploring the effect of region on diversity and composition of weed seedbanks in herbicide-resistant crop systems in the United States.

BACKGROUND: Soil seedbanks have been recognized as one of the crucial components of agricultural ecosystems. However, studies on the shift in structure and biodiversity of soil seedbanks in herbicide-resistant crop systems are limited, and a functional trait perspective of the soil seedbank is often overlooked. RESULTS: A 6 years experiment was conducted to investigate the roles of region, crop system, and weed management strategy on species richness, functional trait diversity, and composition of the weed seedbank. Species richness was different across the interaction of region and crop system, while functional trait diversity only showed difference across regions. Species and functional trait compositions were affected by the interaction of region and crop system. Specifically, the compositional difference among crop systems was mainly determined by the significant heterogeneity of group dispersion. CONCLUSION: Growers and practitioners should consider weed functional traits in developing lasting agricultural management strategies. Long-term weed research should draw attention to the impact of transgenic crop systems and specific management tactics on weed dispersal, functional composition, and resistance evolution of weed species in such agroecosystems. © 2023 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

COVID-19 and postural tachycardia syndrome: a case series.

BACKGROUND: Postural tachycardia syndrome (PTS) is a novel identified sequela of COVID-19 infection. This observational study describes clinical presentation, testing, and treatment response in seven patients diagnosed with PTS following COVID-19 infection. CASE SUMMARY: A total of seven active patients (three collegiate athletes, one recreational athlete, two registered nurses, one hospitality employee), age 24 ± 6 years, and six females were followed for a mean of 152 ± 105 days after contracting COVID-19. Tilt table was performed to establish the diagnosis. The most common presenting symptoms were palpitations (7/7), dyspnoea (6/7), and gastrointestinal complaints (5/7). One patient required hospitalization for symptom management. The mean latency of PTS onset following COVID-19 was 21 ± 15 days. Electrocardiograms (ECGs) demonstrated sinus rhythm in all patients, one with resting sinus tachycardia. Echocardiogram demonstrated normal systolic and diastolic left ventricular function in all patients. On tilt table testing, baseline heart rate (HR) was 72 ± 12 with maximum HR reaching 136 ± 13. Six of seven patients failed to respond to supportive therapy alone, and two patients failed medical management with ivabradine, midodrine, and/or metoprolol. Of three severely symptomatic patients, two demonstrated some degree of clinical recovery with intravenous immunoglobulin (IVIG). DISCUSSION: This novel case series describes the development of PTS in the context of COVID-19 infection. Severity of symptoms and response to treatment was heterogeneous. Interestingly, patients were poorly responsive to traditional PTS treatments, but IVIG showed potential as a possible therapeutic strategy for refractory PTS in two patients, particularly following COVID-19 infection.

Lamins as cancer biomarkers.

Lamins are multifunctional proteins that are often aberrantly expressed or localized in tumours. Here, we endeavour to assess their uses as cancer biomarkers: to diagnose tumours, analyse cancer characteristics and predict patient survival. It appears that the nature of lamin function in cancer is very complex. Lamin expression can be variable between and even within cancer subtypes, which limits their uses as diagnostic biomarkers. Expression of A-type lamins is a marker of differentiated tumour cells and has been shown to be a marker of good or poor patient survival depending on tumour subtype. Further research into the functions of lamins in cancer cells and the mechanisms that determine its patterns of expression may provide more potential uses of lamins as cancer biomarkers.

Utility of salivary gland biopsy in diagnosing Sjogren's syndrome in a POTS patient population.

PURPOSE: POTS patients undergo labial salivary gland biopsies (LSGB) for histologic confirmation of Sjogren's syndrome (SS). Predictive features of positive results are unknown. METHODS: 161 POTS patients underwent LSGB. Their charts were reviewed for antibody and diagnostic testing results. RESULTS: Only 11% (17/161) of POTS patients were SS positive. There were more positive ANA antibodies in those with positive LSGB (65% v 28%, p = .0026). Positive skin nerve biopsy for small fiber neuropathy (SFN) was associated with positive LSGB (p = .046). CONCLUSION: A positive ANA and skin biopsy for SFN are two helpful features in selecting POTS patients for LSGB.

Lamin A: a putative colonic epithelial stem cell biomarker which identifies colorectal tumours with a more aggressive phenotype.

Abnormalities in the expression, distribution and structural organization of A-type lamins are most commonly associated with a spectrum of inherited disorders which predominantly affect mesenchymal lineages, collectively known as laminopathies. However, a new role for lamin A has been discovered in the progression of a common epithelial cancer. CRC (colorectal cancer) patients expressing lamin A/C in their tumour tissue were found to have a 2-fold greater risk of CRC-related mortality compared with patients with lamin A/C-negative tumours. Consequently, lamin A/C is a prognostic biomarker in CRC. In vitro studies suggest that lamin A is an upstream regulator of a pathway linking actin dynamics to loss of cell adhesion, leading to enhanced cell motility and consequently increased invasive potential within a tumour. The finding that lamin A is a putative colonic epithelial stem cell biomarker suggests that the poor outcome associated with lamin A/C-positive tumours may be reflective of a more stem-cell-like phenotype. The present review discusses the link between lamin A expression and tumour progression in one of the commonest causes of cancer-related death in the Western world.

Colonic and colorectal cancer stem cells: progress in the search for putative biomarkers.

The maintenance of healthy colonic crypts is dependent on the integrity of the adult epithelial stem cells located within them. Perturbations in stem cell dynamics are generally believed to represent the first step towards colorectal tumorigenesis. Experimental manipulation of intestinal stem cells has greatly increased our understanding of them, but further progress has been slowed due to the absence of a reliable stem cell biomarker. In this review we discuss the candidate colonic stem cell biomarkers which have been proposed. Furthermore, we investigate the putative biomarkers for so-called colorectal cancer stem cells, a highly aggressive subpopulation of cells considered to drive tumour development.

Spinal anaesthesia with a micro-catheter in high-risk patients undergoing colorectal cancer and other major abdominal surgery.

Extended spinal anaesthesia using a spinal micro-catheter was used as a primary method of anaesthesia for elective colorectal cancer surgery in 68 high risk patients over a 14-year period in our institution. The technique was also useful in eight elective and 13 emergency abdominal surgeries. All patients suffered from severe chronic obstructive airway disease requiring multiple inhalers and drugs (ASA III). Thirty nine of these patients also suffered from angina, myocardial infarction, diabetes and other systemic diseases (ASA IV). Surgery included right hemicolectomy, left hemicolectomy, total colectomy, sigmoid colectomy, Hartman's resection, anterior resection of rectum, abdominoperineal resection, cholecystectomy (open and laparoscopic) and obstructed inguinal hernia requiring laparotomy. Spinal anaesthesia was performed under strict aseptic conditions with a 22 gauge spinal needle with a mixture consisting of 2.75ml of 0.5% heavy bupivacaine and 0.25ml of fentanyl (25microg). This was followed by placement of a spinal micro-catheter and the duration of anaesthesia was extended by intermittent injection of 0.5% isobaric bupivacaine. Brief hypotension occurred in 12.4% of patients during the establishment of anaesthetic block height to T6-7 and was duly treated with intravenous administration of fluid and ephedrine hydrochloride. Good anaesthesia resulted in all patients except for brief discomfort in some patients during hemicolectomy surgery possibly due to the dissection and traction on the peritoneum causing irritation to the diaphragm. The use of sedation was avoided. General anaesthesia was administered in one patient and this patient required postoperative ventilation and cardiovascular support in the Intensive Care Unit. The spinal micro-catheter was removed at the end of surgery. Postoperative pain relief was obtained by administering intravenous morphine through a patient controlled analgesia machine in the critical care ward area (High Dependency Unit). There was a low incidence of minor postoperative side effects such as nausea (14.6%), vomiting (7.9%), minor post dural puncture headache (5.6%) and pruritus (5.6%). We conclude that spinal anaesthesia with a micro-catheter may be used as a primary method of anaesthesia for colorectal cancer surgery and other major abdominal surgery in high-risk patients for whom general anaesthesia would be associated with higher morbidity and mortality.

Comparing the Effects of Two Tillage Operations on Beneficial Epigeal Arthropod Communities and Their Associated Ecosystem Services in Sugar Beets.

Beneficial arthropods provide important ecosystem services in terms of arthropod pest and weed management, but these services can be adversely affected by farming practices such as tillage. This study investigated the impact of two tillage operations (zone tillage and moldboard plow) on the activity density of several beneficial, epigeal arthropod taxa, and postdispersal weed seed and prey removal in sugar beet agroecosystems. In addition, four omnivorous ground beetle species were selected for a weed-seed choice feeding assay, whereas a single species was selected for a weed-seed age preference assay. Ground beetles were the most commonly collected taxon (via pitfall sampling), with only a few dominant species. Tillage operation did not affect ground beetle activity density; however, spider, centipede, and rove beetle activity densities were higher in the reduced-tillage treatment. Live prey consumption was similar between tillage practices, with more prey consumed during nocturnal hours. More weed seeds were consumed in the reduced-tillage treatment, whereas weed-seed preference differed between the four weed species tested [Setaria pumila (Poir.) Roem. & Schult., Echinochloa crus-galli (L.), Kochia scoparia (L.), and Chenopodium album (L.)]. In the weed-seed choice feeding assay, significantly more broad-leaf weed seeds (C. album and K. scoparia) were consumed compared with grassy weed seeds (E. crus-galli and S. pumila). No preference for seed age was detected for E. crus-galli, but Harpalus pensylvanicus (De Geer) preferred old C. album seeds over fresh seeds. Zone tillage is compatible with ecosystem services, providing critical habitat within agricultural ecosystems needed to conserve beneficial, edaphic arthropods.

The challenge of electronic health records (EHRs) design and implementation: responses of health workers to drawing a 'big and rich picture' of a future EHR programme using animated tools.

BACKGROUND AND AIM: To investigate the use of animation tools to aid visualisation of problems for discussion within focus groups, in the context of healthcare workers discussing electronic health records (EHRs). METHOD: Ten healthcare staff focus groups, held in a range of organisational contexts. Each focus group was in four stages: baseline discussion, animator presentation, post-animator discussion and questionnaire. Audio recordings of the focus groups were transcribed and coded and the emergent analytic themes analysed for issues relating to EHR design and implementation. The data allowed a comparison of baseline and post-animator discussion. RESULTS: The animator facilitated discussion about EHR issues and these were thematically coded as: Workload; Sharing Information; Access to Information; Record Content; Confidentiality; Patient Consent; and Implementation. CONCLUSION: We illustrate that use of the animator in focus groups is one means to raise understanding about a proposed EHR development. The animator provided a visual 'probe' to support a more proactive and discursive localised approach to end-user concerns, which could be part of an effective stakeholder engagement and communication strategy crucial in any EHR or health informatics implementation programme. The results of the focus groups were to raise salient issues and concerns, many of which anticipated those that have emerged in the current NHS Connecting for Health Care Records programme in England. Potentially, animator-type technologies may facilitate the user ownership which other forms of dissemination appear to be failing to achieve.

EPSPS Gene Copy Number and Whole-Plant Glyphosate Resistance Level in Kochia scoparia.

Glyphosate-resistant (GR) Kochia scoparia has evolved in dryland chemical fallow systems throughout North America and the mechanism of resistance involves 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) gene duplication. Agricultural fields in four states were surveyed for K. scoparia in 2013 and tested for glyphosate-resistance level and EPSPS gene copy number. Glyphosate resistance was confirmed in K. scoparia populations collected from sugarbeet fields in Colorado, Wyoming, and Nebraska, and Montana. Glyphosate resistance was also confirmed in K. scoparia accessions collected from wheat-fallow fields in Montana. All GR samples had increased EPSPS gene copy number, with median population values up to 11 from sugarbeet fields and up to 13 in Montana wheat-fallow fields. The results indicate that glyphosate susceptibility can be accurately diagnosed using EPSPS gene copy number.

Benchmark study on glyphosate-resistant cropping systems in the United States. Part 7: Effects of weed management strategy (grower practices versus academic recommendations) on the weed soil seedbank over 6 years.

BACKGROUND: Shifts in weed species composition and richness resulting from near-exclusive reliance on herbicides in glyphosate-resistant (GR) cropping systems has necessitated the implementation of alternative weed management tactics to reduce selection pressures of herbicides. We contrasted the response of the weed soil seedbank to effects of weed management strategy, comparing grower practices with academic recommendations for best management practices (BMPs) over 6 years and across five weed hardiness zones in the US Midwest at sites subject to GR cropping systems. RESULTS: Total weed population density and species richness varied according to cropping system, location and prior year's crop, but less so to weed management strategy. The seedbank population density for 11 of the 14 most frequent weed species was affected by weed management strategy either alone or in an interaction with hardiness zone or year, or both. In only 29% of comparisons was weed population density lower following academic recommendations, and this depended upon prior crop and cropping system. The population density of high-risk weed species was reduced by academic recommendations, but only in two of six years and under continuous GR maize. Overall, the weed population density was decreasing in field halves subject to the BMPs in the academic recommendations relative to grower practices. CONCLUSION: The soil seedbank is slow to respond to academic recommendations to mitigate glyphosate-resistant weeds, but represents a biological legacy that growers need to keep in mind even when management practices reduce emerged field weed population densities.

Occurrence of an herbicide-resistant plant trait in agricultural field margins.

Agricultural environments allow study of evolutionary change in plants. An example of evolution within agroecological systems is the selection for resistance to the herbicide glyphosate within the weed, Conyza canadensis. Changes in survivorship and reproduction associated with the development of glyphosate resistance (GR) may impact fitness and influence the frequency of occurrence of the GR trait. We hypothesized that site characteristics and history would affect the occurrence of GR C. canadensis in field margins. We surveyed GR occurrence in field margins and asked whether there were correlations between GR occurrence and location, crop rotation, GR crop trait rotation, crop type, use of tillage, and the diversity of herbicides used. In a field experiment, we hypothesized that there would be no difference in fitness between GR and glyphosate-susceptible (GS) plants. We asked whether there were differences in survivorship, phenology, reproduction, and herbivory between 2 GR and 2 GS populations of C. canadensis in agrestal and ruderal habitats. We found that geographic location was an important factor in the occurrence of GR C. canadensis in field margins. Although not consistently associated with either glyphosate resistance or glyphosate susceptibility, there were differences in phenology, survivorship, and herbivory among biotypes of C. canadensis. We found equal or greater fitness in GR biotypes, compared to GS biotypes, and GR plants were present in field margins. Field margins or ruderal habitats may provide refugia for GR C. canadensis, allowing reproduction and further selection to occur as seeds recolonize the agrestal habitat. Agricultural practices may select for ecological changes that feed back into the evolution of plants in ruderal habitats.

An exploratory study of what clients like least about assertive community treatment.

As part of a larger interview, clients of assertive community treatment programs answered an open-ended question about what they liked least about assertive community treatment. Of 182 clients, 44 percent reported that they disliked nothing; 21 percent said that they disliked features that are considered specific to assertive community treatment, such as home visits, or that have been criticized in the literature, such as intrusiveness; 16 percent said that they were dissatisfied with underimplementation of elements thought to characterize assertive community treatment, such as frequency of visits; and 19 percent said that they were dissatisfied with general aspects of mental health service delivery, such as an inconvenient office location. Compared with clients of programs with low levels of fidelity to assertive community treatment, clients of high-fidelity programs had fewer complaints overall and fewer complaints about features considered to be specific to assertive community treatment.

Benchmark study on glyphosate-resistant crop systems in the United States. Economics of herbicide resistance management practices in a 5 year field-scale study.

BACKGROUND: Since the introduction of glyphosate-resistant (GR) crops, growers have often relied on glyphosate-only weed control programs. As a result, multiple weeds have evolved resistance to glyphosate. A 5 year study including 156 growers from Illinois, Iowa, Indiana, Nebraska, North Carolina and Mississippi in the United States was conducted to compare crop yields and net returns between grower standard weed management programs (SPs) and programs containing best management practices (BMPs) recommended by university weed scientists. The BMPs were designed to prevent or mitigate/manage evolved herbicide resistance. RESULTS: Weed management costs were greater for the BMP approach in most situations, but crop yields often increased sufficiently for net returns similar to those of the less expensive SPs. This response was similar across all years, geographical regions, states, crops and tillage systems. CONCLUSIONS: Herbicide use strategies that include a diversity of herbicide mechanisms of action will increase the long-term sustainability of glyphosate-based weed management strategies. Growers can adopt herbicide resistance BMPs with confidence that net returns will not be negatively affected in the short term and contribute to resistance management in the long term.

Metastatic breast carcinoma presenting as a sigmoid stricture: report of a case and review of the literature.

Metastatic spread of breast carcinoma to the colon and rectum is rare. We report the case of a patient treated for lobular breast carcinoma presenting 17 years later with metastatic breast cancer of the colon. A 63-year-old lady with a past history of right-sided invasive lobular carcinoma of the breast presented with persistent diarrhoea. Colonoscopy with biopsies revealed a benign-looking stricture at the rectosigmoid junction. A CT scan of the abdomen and pelvis revealed a benign-looking stricture in keeping with a probable diverticular stricture. A Hartmann procedure was performed and histology revealed a metastatic lobular carcinoma with oestrogen and progesterone receptor-positive status. Treatment was commenced with letrozole and the patient remains well under clinical surveillance. In a patient with a history of breast carcinoma who presents with gastrointestinal symptoms the possibility of gastrointestinal tract spread should always be considered. Endoscopic diagnosis may be misleading with pathological diagnosis only being made following surgical resection. A history of breast carcinoma must be declared to the histopathologist following surgical resection so that an accurate diagnosis is made and appropriate treatment is commenced.

The role of Lamin A in cytoskeleton organization in colorectal cancer cells: a proteomic investigation.

Up-regulated expression of lamin A has been implicated in increased cell invasiveness and mortality in colorectal cancer. Here we use quantitative proteomics to investigate lamin A regulated changes in the cytoskeleton that might underpin increased cell motility. Using siRNA knockdown of lamin A in a model cell line (SW480/lamA) we confirm that the presence of lamin A promotes cell motility. Using an enhanced technique to prepare cytoskeleton fractions in combination with 2D DiGE we were able to accurately and reproducibly detect changes in the representation of protein species within the cytoskeleton as low as 20%. In total 64 protein spots displayed either increased or decreased representation within the cytoskeleton of SW480/lamA cells compared to controls. Of these the identities of 29 spots were determined by mass spectrometry. A majority were multiple forms of three classes of proteins, including components of the actin and IF cytoskeletons, protein chaperones and translation initiation and elongation factors. In particular our data reveal that the representation of tissue transglutaminase 2, which is known to modify elements of the cytoskeleton and is associated with cancer progression, was highly over-represented in the cytoskeleton fraction of SW480/lamA cells. Overall, our data are consistent with changed protein cross-linking and folding that favours the formation of dynamic actin filaments over stress fibres accounting for the altered cell motility properties in SW480/lamA cells.

Benchmark study on glyphosate-resistant crop systems in the United States. Part 2: Perspectives.

A six-state, 5 year field project was initiated in 2006 to study weed management methods that foster the sustainability of genetically engineered (GE) glyphosate-resistant (GR) crop systems. The benchmark study field-scale experiments were initiated following a survey, conducted in the winter of 2005-2006, of farmer opinions on weed management practices and their views on GR weeds and management tactics. The main survey findings supported the premise that growers were generally less aware of the significance of evolved herbicide resistance and did not have a high recognition of the strong selection pressure from herbicides on the evolution of herbicide-resistant (HR) weeds. The results of the benchmark study survey indicated that there are educational challenges to implement sustainable GR-based crop systems and helped guide the development of the field-scale benchmark study. Paramount is the need to develop consistent and clearly articulated science-based management recommendations that enable farmers to reduce the potential for HR weeds. This paper provides background perspectives about the use of GR crops, the impact of these crops and an overview of different opinions about the use of GR crops on agriculture and society, as well as defining how the benchmark study will address these issues.

Benchmark study on glyphosate-resistant cropping systems in the United States. Part 5: Effects of glyphosate-based weed management programs on farm-level profitability.

BACKGROUND: Glyphosate-resistant (GR) crops have changed the way growers manage weeds and implement control strategies. Since the introduction of GR crops, growers in many instances have relied on glyphosate almost exclusively to control a broad spectrum of weeds. This over-reliance on glyphosate has resulted in the evolution of glyphosate resistance in some weed species. Growers and scientists are concerned about the sustainability of GR crops and glyphosate. When a grower is making decisions about weed control strategies, economic costs and benefits of the program are primary criteria for selection and implementation. Studies across six states were initiated in 2006 to compare the economics of using a weed resistance best management practice (BMP) system with a grower's standard production system. RESULTS: Resistance BMP systems recommended by university scientists were more costly but provided similar yields and economic returns. Rotation of GR crops resulted in a higher net return (maize and soybean) compared with continuous GR crop (cotton or soybean) or rotating a GR crop with a non-GR crop (maize). CONCLUSION: Growers can implement weed resistance BMP systems with the confidence that their net returns will be equivalent in the short run, and, in the long term, resistance BMP systems will prevent or delay the evolution of GR weeds in their fields, resulting in substantial savings.

Benchmark study on glyphosate-resistant cropping systems in the United States. Part 1: Introduction to 2006-2008.

Glyphosate-resistant (GR) crop technology has dramatically impacted agriculture. The adoption of GR systems in canola, maize, cotton, soybean and sugar beets has been widespread in the United States. However, weed scientists are concerned that growers' current herbicide programs and weed management tactics will affect their sustainability and effectiveness. Without proper management, the potential for weed populations to express a high degree of resistance to glyphosate will adversely impact the utility of glyphosate. In 2005, weed scientists from six universities initiated a long-term research study to assess the sustainability of GR technology. This paper introduces five other articles in this series. Over 150 fields of at least 10 ha were selected to participate in a long-term field-scale study, and each field was split in half. On one-half the grower continued using the current weed management program; on the other half the grower used academic-recommended herbicide resistance best management practices. Field data were collected in 2006-2008 to determine the impact of the two weed management programs on weed populations, diversity, seedbank, crop yields and economic returns. This long-term study will provide invaluable data for determining the sustainability and profitability of diversified weed management programs designed to lower the risk of evolving weed resistance to glyphosate.