New Leaf Center

The aim of this study was to evaluate the feasibility of reimbursing medical cannabis for chronic pain within a workers' compensation framework. A program evaluation was conducted by the Colorado Division of Workers' Compensation's Alternative Pain Management Program to assess the feasibility of medical cannabis reimbursement. The program included medical cannabis, care coordination, and robust clinical oversight. Outcome measures were collected at baseline and over 12 months. The program demonstrated the feasibility of reimbursing medical cannabis under a coordinated care model. Upon program completion, the patient reported meaningful reductions in pain, improvement in function, increased quality of life, and psychosocial stability. A modest reduction in opioid use was observed. No adverse safety events occurred. This program evaluation suggests that medical cannabis reimbursement may be a viable option for very select workers' compensation patients.

Differences between near-infrared (NIR) spectroscopyinstrumentsmake it difficult to apply calibration models universally across multipleinstruments; hence, calibration transfer (CT) is crucial. To ensurethat a model developed on one instrument is also applicable to a newinstrument, this study establishes a CT method based on nonparametrictechniques, referred to as nonparametric varying-coefficient regressioncalibration transfer (NVT). This method uses a varying-coefficientmodel (VCM) to build a functional relationship between the masterand slave spectra using a set of standard sample spectra and employsB-splines as basis functions for function fitting. This functionalrelationship helps transfer the slave spectra of other samples intothe master spectra, reducing the spectral differences caused by instrumentvariations. The performance of NVT was tested on the determinationof moisture, oil, protein, and starch in corn, and the content oftotal plant alkaloids, reducing sugars, total sugars, and total nitrogenin tobacco using NIR spectroscopy. NVT was compared with two commonCT methods: spectral space transformation (SST) and piecewise directstandardization (PDS). The results show that NVT can effectively eliminatesome spectral differences caused by different instruments and significantlyimprove analytical accuracy. Compared with that of PDS, the CT effectof NVT is significantly improved, whereas compared with that of SST,it is slightly improved. This method is insensitive to parameters,making it easy to select parameters and providing a new idea for CTmethod design.

KPTN-related disorder is an autosomal recessive disorder associated with germline variants in KPTN (previously known as kaptin), a component of the mTOR regulatory complex KICSTOR. To gain further insights into the pathogenesis of KPTN-related disorder, we analysed mouse knockout and human stem cell KPTN loss-of-function models.Kptn−/− mice display many of the key KPTN-related disorder phenotypes, including brain overgrowth, behavioural abnormalities, and cognitive deficits. By assessment of affected individuals, we have identified widespread cognitive deficits (n = 6) and postnatal onset of brain overgrowth (n = 19). By analysing head size data from their parents (n = 24), we have identified a previously unrecognized KPTN dosage-sensitivity, resulting in increased head circumference in heterozygous carriers of pathogenic KPTN variants.Molecular and structural analysis of Kptn−/− mice revealed pathological changes, including differences in brain size, shape and cell numbers primarily due to abnormal postnatal brain development. Both the mouse and differentiated induced pluripotent stem cell models of the disorder display transcriptional and biochemical evidence for altered mTOR pathway signalling, supporting the role of KPTN in regulating mTORC1.By treatment in our KPTN mouse model, we found that the increased mTOR signalling downstream of KPTN is rapamycin sensitive, highlighting possible therapeutic avenues with currently available mTOR inhibitors. These findings place KPTN-related disorder in the broader group of mTORC1-related disorders affecting brain structure, cognitive function and network integrity.

Abstract KPTN-related disorder (KRD) is an autosomal recessive disorder associated with germline variants in KPTN (kaptin), a component of the mTOR regulatory complex KICSTOR. To gain further insights into the pathogenesis of KRD, we analysed mouse knockout and human stem cell KPTN loss-of-function models. Kptn−/− mice display many of the key KRD phenotypes, including brain overgrowth, behavioural abnormalities, and cognitive deficits. Assessment of affected individuals has identified concordant selectivity of cognitive deficits, postnatal onset of brain overgrowth, and a previously unrecognised KPTN dosage-sensitivity, resulting in increased head circumference in their heterozygous parents. Molecular and structural analysis of Kptn−/− mice revealed pathological changes, including differences in brain size, shape, and cell numbers primarily due to abnormal postnatal brain development. Both the mouse and differentiated iPSC models of the disorder display transcriptional and biochemical evidence for altered mTOR pathway signalling, supporting the role of KPTN in regulating mTORC1. Increased mTOR signalling downstream of KPTN is rapamycin sensitive, highlighting possible therapeutic avenues with currently available mTOR inhibitors. These findings place KRD in the broader group of mTORC1 related disorders affecting brain structure, cognitive function, and network integrity.

A field study was conducted to examine sand texture and root zone amendment effects on soil water fate, focusing particularly on turfgrass water use. Six root zone treatments were used, each with a depth of 0.3 m overlying a 0.1‐m thick gravel layer. Two were 100% sand where the sands were relatively finer and coarser, two used the same sands blended to contain 90% sand and 10% sphagnum peat (by volume), and the final two root zones were blended by adding 10% soil to the sand:peat mixes. While supporting ‘Penncross’ creeping bentgrass (Agrostis palustris Huds.), a water balance accounting was conducted during the growing seasons of 2000 and 2001. This involved daily measurement of rainfall, irrigation, drainage volume, and soil water contents with turfgrass evapotranspiration (ET) determined as the change in water content within the root zone plus rain or irrigation depths and minus the drainage depths. Turfgrass rooting was measured in the first week of October each year, and water retention curve and saturated hydraulic conductivity measurements were conducted in the fall of 2001. Overall, the results of the field experiment showed that increasing amendment amounts to either sand yielded significantly greater water retention, reduced saturated hydraulic conductivity, and greater root zone water contents; however, the sand and amendment treatments had little consistent effect on turfgrass response as judged by actual ET and rooting measurements.

Although bacteriophage Mu cannot infect Erwinia stewartii, lysogens were constructed by conjugal transfer of an RK2::Mu cts 62 hybrid plasmid, pRK210, into this species from Escherichia coli. The pRK210 transconjugants were stable and produced infectious Mu virions. The Mu cts 62 prophage was thermally induced at 42°C and zygotically induced following transfer of the plasmid to E. stewartii recipients. Induction was accompanied by an increased frequency of Gal− and Thy− mutants among the survivors. Mu promises to be an important tool for studying the genetics of pathogenicity in E. stewartii.

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