Preferred Option Research Articles

Metabolic Reprogramming in Gliocyte Post-cerebral Ischemia/ Reperfusion: From Pathophysiology to Therapeutic Potential.

Ischemic stroke is a leading cause of disability and death worldwide. However, the clinical efficacy of recanalization therapy as a preferred option is significantly hindered by reperfusion injury. The transformation between different phenotypes of gliocytes is closely associated with cerebral ischemia/ reperfusion injury (CI/RI). Moreover, gliocyte polarization induces metabolic reprogramming, which refers to the shift in gliocyte phenotype and the overall transformation of the metabolic network to compensate for energy demand and building block requirements during CI/RI caused by hypoxia, energy deficiency, and oxidative stress. Within microglia, the pro-inflammatory phenotype exhibits upregulated glycolysis, pentose phosphate pathway, fatty acid synthesis, and glutamine synthesis, whereas the anti-inflammatory phenotype demonstrates enhanced mitochondrial oxidative phosphorylation and fatty acid oxidation. Reactive astrocytes display increased glycolysis but impaired glycogenolysis and reduced glutamate uptake after CI/RI. There is mounting evidence suggesting that manipulation of energy metabolism homeostasis can induce microglial cells and astrocytes to switch from neurotoxic to neuroprotective phenotypes. A comprehensive understanding of underlying mechanisms and manipulation strategies targeting metabolic pathways could potentially enable gliocytes to be reprogrammed toward beneficial functions while opening new therapeutic avenues for CI/RI treatment. This review provides an overview of current insights into metabolic reprogramming mechanisms in microglia and astrocytes within the pathophysiological context of CI/RI, along with potential pharmacological targets. Herein, we emphasize the potential of metabolic reprogramming of gliocytes as a therapeutic target for CI/RI and aim to offer a novel perspective in the treatment of CI/RI.

Multi-Objective Optimization Methods for Train Load Planning in Seaport Container Terminals

In this paper we study the planning problem of loading trains in seaport container terminals, which consists in assigning containers to the wagon slots. The train load can be realized considering different objectives, in this work we focus on two very important objectives for terminal managers, that are the minimization of the number of reshuffles in the storage area and the minimization of the total distance covered by the handling equipment between the storage area and the wagons. To address this problem, some multi-objective methods are investigated in the paper, based on the <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\varepsilon$</tex-math> </inline-formula> -constraint approach and the lexicographic algorithm, allowing to find different sets of efficient solutions to be provided to train planners. The experimental tests, devised to compare the proposed multi-objective methods, show that the <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\varepsilon$</tex-math> </inline-formula> -constraint method integrated with a lexicographic approach is the most efficient choice since it allows to obtain a higher number of efficient solutions in shorter computational times. This method can be applied in decision support systems for train planners in order to allow them to decide the train load in an efficient way. <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Note to Practitioners</i> —The automation and the process optimization in seaport container terminals is a relevant issue for terminal managers in order to face the strong competitiveness in the logistics and shipping sector and the new emerging problems due to the presence of mega vessels. Among the different operations to be optimally managed in a terminal, the loading of trains is becoming more and more significant, also due to the increase of freight traffic by rail, seen as a cheaper and more sustainable option compared with road transport. The optimal assignment of containers present in a storage area to the wagon slots is a crucial decision in order to reduce operational times and costs in a container terminal. In this paper, we address the train load planning problem considering two important objectives to be minimized, i.e. the number of reshuffles and the distance covered by the handling equipment. The multi-objective methods proposed in the paper are devised to find different efficient solutions in short computational times. The proposed algorithms are intended to be implemented within a decision support tool in which the solutions found are shown to the train planner who chooses the preferred option depending on personal evaluations and on the basis of information coming in real time.

Application of Platelet-Rich Plasma as a Stem Cell Treatment - an Attempt to Clarify a Common Public Misconception.

In recent years, there has been a significant increase in the practice of regenerative medicine by health practitioners and direct-to-consumer businesses globally. Among different tools of regenerative medicine, platelet-rich plasma (PRP) and stem cell-based therapies have received considerable attention. The use of PRP, in particular, has gained popularity due to its easy access, simple processing techniques, and regenerative potential. However, it is important to address a common misconception amongst the general public equating to PRP and stem cells due to the demonstrated efficacy of PRP in treating musculoskeletal and dermatological disorders. Notably, PRP promotes regeneration by providing growth factors or other paracrine factors only. Therefore, it cannot replenish or replace the lost cells in conditions where a large number of cells are required to regenerate tissues and/or organs. In such cases, cellbased therapies are the preferred option. Additionally, other tools of regenerative medicine, such as bioprinting, organoids, and mechanobiology also rely on stem cells for their success. Hence, healthcare and commercial entities offering direct-to-customer regenerative therapies should not mislead the public by claiming that the application of PRP is a stem cell-based therapy. Furthermore, it is important for regulatory bodies to strictly monitor these profit-driven entities to prevent them from providing unregulated regenerative treatments and services that claim a broad variety of benefits with little proof of efficacy, safety concerns, and obscure scientific justification.

Thermal creep properties of virgin and irradiated cladding tubes made of Ti-stabilised DIN 1.4970 (15-15Ti) austenitic stainless steel

ABSTRACT This paper presents assessments performed on a large database of virgin material and irradiated material thermal creep data from uniaxial and pressurised DIN 1.4970 Ti-stabilised austenitic stainless steel i.e. EN X10NiCrMoTiB15–15 or ‘15-15Ti’ cladding tubes. The data base incorporates multi-heat data from uniaxial and bi-axial (internal pressure) creep tests conducted during the fast reactor R&D program of the DeBeNe (Deutschland-Belgium-Netherlands) consortium between the 1960s to the late 1980s together with more recent data, for example, from the European projects MATTER and PATRICIA and the EERA JPNM pilot project TASTE. The data comprises of a virgin material data base and a data base with irradiated creep data. The virgin material data comprises of time-to-rupture and time-to-0.2% creep strain in a temperature range of 600–800°C and covers a large range of stresses. The irradiated data base has less data and does not cover all material heats tested for the virgin material properties. The irradiation conditions are also different depending on the test reactor specifics and the irradiation campaign targets. The attained ‘irradiation damage’ in displacements per atom (DPA) for the irradiated materials range from 0.1 up to 38.1. Un-irradiated ‘reference material’ models for tensile strength and creep strength are constructed from the current-state of the art literature data and more recent results from the Sandvik 24% cold worked 1515–Ti cladding tube currently used as the main material batch studied at SCK CEN. The tensile strength model is used throughout the paper for normalizing creep strengths by the tensile properties, needed when applying the Wilshire (WE) creep model. Time factors (TF), stress factors (SF) and temperature ratio factors (TRF) are calculated for different material states for describing the impact of heat treatments, (virgin and irradiated) and irradiation conditions. This initial study targets to give estimates for the thermal creep properties of cladding tubes with a cold work range of 16–24% in a non-annealed state, as it is the preferred option for future designs according to the state-of-the art knowledge base. However, the main bulk of the available data on irradiated material is on claddings with a cold work range of 0-16% with and without annealing and at various levels of irradiation damage, thus leading to the need for estimation by interpolation and extrapolation assuming that irradiation damage levels and trends, e.g. time reduction factors found on a lower cold worked material can also be applied on materials with higher cold work levels. The results of the assessments clearly show relative strength differences between chosen material heats and heat treatments and has enabled constructing simple multilinear models for estimating the life of irradiated material. The models show that low creep test temperatures (and irradiation temperatures), low stress levels, low levels of cold work and high irradiation doses are increasing the detrimental difference between the specific material condition and the reference material. Also, it was found that the general level of life reduction (time factor TF and stress factor SF) for irradiation damaged material failure, in relation to the reference material failure, roughly coincides the corresponding values of time to 0.2% creep strain for virgin material. The estimated ‘failure creep temperature limits’ for 30 000 hours of service are studied and compared for both virgin and irradiated materials at a reference stress level of 1/3 of the tensile strength (at temperature).

PCV Adjuvant Therapy as a Preferred Treatment Option for Oligodendroglioma Patients: A Comparative Study With Temozolomide and Concurrent Radiotherapy

INTRODUCTION: When treating oligodendroglioma patients, choosing between temozolomide (TMZ) and procarbazine, lomustine, and vincristine (PCV), with concurrent radiotherapy still poses a challenge. Given the commonality of tumor recurrence, optimizing progression-free survival while minimizing adverse effects is crucial to improving quality of life. METHODS: 87 patients treated for oligodendroglioma between 1994-2022 were retrospectively reviewed. Progression-free survival (PFS) and overall survival (OS) from initial resection were compared between PCV-based or TMZ-based treatment groups using Kaplan-Meier and multi-variable Cox survival analysis. RESULTS: The median age at diagnosis was 41 years and 62% were male. After initial resection, 42.8% received PCV-based treatment and 57.2% received TMZ-based treatment. Treatment groups were balanced in terms of age, tumor genetic profiling, extent of resection, or KPS score, however, the TMZ-based group had more patients receiving concurrent radiation. The entire cohort had a 6.3-year PFS and 21.0-year OS. The median time to recurrence was significantly longer in those treated with PCV (12 years) compared to those treated with TMZ (4.7 years). PFS [HR = 0.46, p = 0.04] and OS [HR = 0.26, p = 0.04] were significantly longer for those receiving PCV-based treatment compared to TMZ-based treatment. After adjusting for factors mentioned above, Cox regression analysis revealed no difference in OS between PCV- and TMZ-based treatment. The overall adverse effect rate did not significantly differ between PCV-based and TMZ-based treatment (25% vs. 28.1%, p &gt; 0.99). CONCLUSIONS: PCV confers improved progression-free survival than TMZ-based treatment for oligodendroglioma patients, noting that most patients in our series received concurrent radiation with TMZ, and those receiving PCV not having received upfront radiation. As we anticipate the results of the CODEL trial, our findings suggest PCV-based therapy warrants consideration as a preferred therapeutic option for oligodendroglioma patients.

Liver transplantation for hepatocellular carcinoma in India: Are we ready for 2040?

Liver transplantation (LT) for hepatocellular carcinoma (HCC) has been widely researched and is well established worldwide. The cornerstone of this treatment lies in the various criteria formulated by expert consensus and experience. The variations among the criteria are staggering, and the short- and long-term out comes are controversial. To study the differences in the current practices of LT for HCC at different centers in India and discuss their clinical implications in the future. We conducted a survey of major centers in India that performed LT in December 2022. A total of 23 responses were received. The centers were classified as high- and low-volume, and the current trend of care for patients und ergoing LT for HCC was noted. Of the 23 centers, 35% were high volume center (> 500 Liver transplants) while 52% were high-volume centers that performed more than 50 transplants/year. Approximately 39% of centers had performed > 50 LT for HCC while the percent distribution for HCC in LT patients was 5%-15% in approximately 73% of the patients. Barring a few, most centers were divided equally between University of California, San Francisco (UCSF) and center-specific criteria when choosing patients with HCC for LT, and most (65%) did not have separate transplant criteria for deceased donor LT and living donor LT (LDLT). Most centers (56%) preferred surgical resection over LT for a Child A cirrhosis patient with a resectable 4 cm HCC lesion. Positron-emission tomography-computed tomography (CT) was the modality of choice for metastatic workup in the majority of centers (74%). Downstaging was the preferred option for over 90% of the centers and included transarterial chemoembolization, transarterial radioembolization, stereotactic body radiotherapy and atezolizumab/bevacizumab with varied indications. The alpha-fetoprotein (AFP) cut-off was used by 74% of centers to decide on transplantation as well as to downstage tumors, even if they met the criteria. The criteria for successful downstaging varied, but most centers conformed to the UCSF or their center-specific criteria for LT, along with the AFP cutoff values. The wait time for LT from down staging was at least 4-6 wk in all centers. Contrast-enhanced CT was the preferred imaging modality for post-LT surveillance in 52% of the centers. Approximately 65% of the centers preferred to start everolimus between 1 and 3 months post-LT. The current predicted 5-year survival rate of HCC patients in India is less than 15%. The aim of transplantation is to achieve at least a 60% 5-year disease free survival rate, which will provide relief to the prediction of an HCC surge over the next 20 years. The current worldwide criteria (Milan/UCSF) may have a higher 5-year survival (> 70%); however, the majority of patients still do not fit these criteria and are dependent on other suboptimal modes of treatment, with much lower survival rates. To make predictions for 2040, we must prepare to arm ourselves with less stringent selection criteria to widen the pool of patients who may undergo transplantation and have a chance of a better outcome. With more advanced technology and better donor outcomes, LDLT will provide a cutting edge in the fight against liver cancer over the next two decades.

Experimental assessment of the exposure to airborne exhaled contaminants using general and personalised ventilation systems in a hospital room

Ensuring good indoor air quality is critical in hospitals. An environment free from airborne particles can prevent the spread of various diseases and improve patient health. In this study, the efficiency of a personalised ventilation supply system (PSS) and personalised ventilation extraction system (PES) for diluting and removing contaminants exhaled by a patient in a hospital bed was evaluated. These systems, which were integrated into the head and foot of a hospital bed, were combined with three general ventilation strategies in the room. Fifteen ventilation strategies were analysed experimentally. Two breathing thermal manikins (BTMs) were used to simulate a patient and health worker in a hospital. The breathing of each BTM was controlled by the patient (source) generating particles that can increase the risk of infection in a healthy person (target). Experimental results show that using a PES combined with general ventilation of the room reduces the exposure of the target manikin compared to general ventilation strategies alone. However, no marked improvement was observed when the PSS was activated. The reduction in exposure to the target manikin was considerable when the PES was located at the foot of the hospital bed, which is the preferred option for integrating personalised systems in a hospital bed.

Percutaneous microwave ablation of T1a renal cell carcinomas: A 10-year single-center retrospective review.

Partial nephrectomy is currently the preferred treatment option for T1a renal cell carcinomas (RCC), with nephron-sparing techniques, including microwave ablation, becoming more common in select patients. Primary aims are to document outcomes of microwave ablation for T1a RCCs in an Australian tertiary centre to add to the evidence for its safety and efficacy. The prospectively maintained Sir Charles Gairdner Hospital Interventional Radiology database was retrospectively searched for all Renal Microwave ablations completed between June 2012 and February 2022. This database and a combination of hospital programmes including Agfa Impax PACS, Bossnet digital medical record and iSoft Clinical Manager were used to extract the relevant data which was anonymized and entered into an Excel spreadsheet for analysis. Forty-eight patients underwent microwave ablation for 50 tumours. Of these, there were two local and two distant recurrences. A fifth patient had metastases on presentation. Higher local recurrence rates were associated with larger tumour size (P = 0.043). Tumour proximity to the collecting system <4 mm was associated with higher rates of complications (P = 0.020). RENAL scores did not show statistically significant correlation with complications (P = 0.092) or local or distant recurrence. Notably, the study follow-up time was longer than many comparative studies (mean = 2796, ~7.66 years censoring for death and mean = 832 days, ~2.28 years not censoring for death). Consistent with the literature, this study further demonstrates that microwave ablation is a safe and efficacious option for treatment of T1a RCC.

Rosamultin ameliorates radiation injury via promoting DNA injury repair and suppressing oxidative stress in vitro and in vivo

Radiotherapy remains the preferred treatment option for cancer patients with the advantages of broad indications and significant therapeutic effects. However, ionizing radiation can also damage normal tissues. Unfortunately, there are few anti-radiation damage drugs available on the market for radiotherapy patients. Our previous study showed that rosamultin had antioxidant and hepatoprotective activities. However, its anti-radiation activity has not been evaluated. Irradiating small intestinal epithelial cells and mice with whole-body X-rays radiation were used to evaluate the in vitro and in vivo effects of rosamultin, respectively. Intragastric administration of rosamultin improved survival, limited leukocyte depletion, and reduced damage to the spleen and small intestine in irradiated mice. Rosamultin reversed the downregulation of the apoptotic protein BCL-2 and the upregulation of BAX in irradiated mouse small intestine tissue and in irradiation-induced small intestinal epithelial cells. DNA-PKcs antagonists reversed the promoting DNA repair effects of rosamulin. Detailed mechanistic studies revealed that rosamultin promoted Translin-associated protein X (TRAX) into the nucleus. Knockdown of TRAX reduced the protective effect of rosamultin against DNA damage. In addition, rosamultin reduced irradiation-induced oxidative stress through promoting Nrf2/HO-1 signaling pathway. To sum up, in vitro and in vivo experiments using genetic knockdown and pharmacological activation demonstrated that rosamultin exerts radioprotection via the TRAX/NHEJ and Nrf2/HO pathways.

External Wall Systems in Passive House Standard: Material, Thermal and Environmental LCA Analysis

The construction sector, a significant consumer of energy, possesses the potential to realize substantial environmental and economic advantages through the adoption of innovative technologies and design approaches. Notably, the Passive House standard, exemplified by energy-efficient single-family homes, emerges as a prominent solution. This study analyzes five external wall systems across multiple stages: (i) a literature review and examination of external wall techniques within the passive standard, utilizing the Passive House Database; (ii) a material and technological assessment of three wood-based and two masonry constructions; (iii) an in-depth thermal performance analysis of selected external partitions; and (iv) a Life Cycle Assessment (LCA) of the external wall systems. Our findings indicate that among the single-family homes built to the passive standard, 50.94% utilized timber constructions, while 34.21% employed masonry. Thermal analysis revealed that the masonry wall, EW-M-01, exhibited superior thermal efficiency with a heat transfer coefficient (U-value) of 0.0889 W/m2K. Meanwhile, the wooden wall, EW-T-01, led its category with a U-value of 0.1000 W/m2K. The LCA highlighted that the wooden wall EW-T-02 presented the lowest integrated non-renewable energy demand (PENTR) at 425.70 MJ/kg and the most favorable Global Warming Potential (GWP), with a reduction of 55.51 kg CO2e. Conversely, the masonry wall EW-M-01 recorded the highest energy demand and CO2e emissions, at 780.96 MJ/kg and 90.59 kg CO2e, respectively. Water consumption was lowest for the EW-T-02 wooden wall (0.08 m3) and highest for the EW-M-02 masonry wall (0.19 m3). Conclusively, our analysis of passive house external walls demonstrates that wood-based systems offer superior performance in terms of materials, thermal efficiency, and LCA indicators, positioning them as the preferred option for sustainable passive construction.

Challenges faced by learners with multiple disabilities at a resource school in the Oshana region of Namibia

AbstractUpon attaining freedom from the South African regime in 1990, Namibia adopted a constitution according to which access to education is a fundamental right. Before the Salamanca Statement in 1994 and Namibia's consequent ratification thereof, education in Namibia was mainly divided into two distinct streams: general education and special education. Post‐Salamanca, there has been a slight shift in the provision of education for learners with special educational needs in that special education was, and mainly continues to be, offered in special schools, now called resource schools; in special classes and units attached to regular schools; and in mainstream classrooms with an inclusive education orientation. Learners with severe to profound special educational needs are mainly educated in resource schools, and this remains the preferred option for most parents and communities of children with severe to profound special needs. The resource schools are constructed for a specific set of disabilities, such as sensory, physical or intellectual disabilities. They are assumed to be well‐equipped with material and personnel resources that enable staff to respond effectively to the needs of their learners. Most, if not all, the resource schools in Namibia were built a long time ago, to serve a specific population of learners. However, some learners present with a range of disabilities and barriers to learning that could be beyond the original scope of the specific school. Consequently, more and more teachers in resource schools report that they observe daily how learners struggle to function in schools in which the infrastructure and resources can barely accommodate their complex needs. This is mainly because of the diversity and comorbid conditions of these learners. This research focused on the challenges encountered by learners with multiple disabilities in a resource school for learners with sensory disabilities. The study followed a qualitative approach, with an intrinsic case study design. Purposive, criterion sampling procedures were employed to select the participants. Data were collected through semi‐structured, face‐to‐face, in‐depth interviews, complemented by observation. The main findings of the study are that learners with multiple disabilities faced challenges associated with the physical infrastructure of the school (accessibility), the inability of staff to respond effectively to their needs, a lack of teaching and learning resources (leading to their exclusion from certain learning activities), as well as a poorly structured curriculum that undermines their multiple disabilities. The research reveals that there is limited agency and acknowledgement of the complex needs of children with multiple disabilities. The study concludes that learners with multiple disabilities need to access a curriculum that is cognisant of their needs and receive the quality education that they deserve, as set out in the Sector Policy on Inclusive Education. In addition to the curriculum, the school environment should be welcoming and stigma‐free, to enable learners to experience a sense of belonging, love and security. We recommend an audit of the needs of learners with multiple disabilities in order to create a conducive learning and socialisation environment for them. Furthermore, the government could invest in renovating old buildings, as well as adjusting infrastructure to the complex needs of learners, so that resource schools can become more inclusive by identifying and responding to the needs of all learners.

Evaluation of the drug-drug interaction between triazole antifungals and cystic fibrosis transmembrane conductance regulator modulators in a real-life cohort.

Limited data on the clinical management of drug-drug interactions between triazoles and Cystic Fibrosis transmembrane conductance regulator (CFTR) modulators are available. We retrospectively evaluated azole target attainment and dose adaptations in patients from two Dutch CF centres concomitantly receiving triazoles and CFTR modulators. In total, 21 patients with 59 triazole trough concentrations were evaluated. Subtherapeutic concentrations were frequently observed, especially for itraconazole and voriconazole. Of the investigated antifungal agents, posaconazole appears the most preferable option. Our results emphasize the importance of adequate management of this interaction and underpin the added value of therapeutic drug monitoring of triazoles in this population.

Policy analysis for sustainable EV charging facility adoption using SEM-ANN approach

Researchers often reported that the non-availability of public charging infrastructure is the primary concern in adopting electric vehicles (EVs) in India. Adopting a home charging facility would help at the preliminary stage of EV introduction, where there is less scope for public charging infrastructure. In addition, integrating the solar rooftop photovoltaic (PV) facility to generate electricity for EV charging would help to develop a sustainable change in the transport sector. Thus, this study aims to identify various influencing factors that affect individual householder's decisions to adopt a home charging facility supported by a rooftop PV system for EV charging. Also, this study identifies and prioritises the most suitable policy options to encourage users to adopt EVs, including home EV charging supported by rooftop PV facilities. For this purpose, a questionnaire survey was conducted with individual householders in Ahmedabad, India, and 850 samples were used for the analysis. An integrated partial least squares-structural equation modelling with the artificial neural network method was adopted in this study. The study's findings reveal that the comfort and convenience of charging a vehicle at home, reduced range anxiety, comparatively lesser charging cost, flexibility to charge the vehicle, and no waiting to charge the vehicle are significant motivating factors for adopting a home charging facility. The willingness to adopt a rooftop PV system positively influences EV charging at home. In addition, providing a combined incentive to install home EV charging and a rooftop PV facility is the most preferred policy option. The outcome of this study would significantly help transport planners, policymakers, and researchers develop effective strategies and policies to boost EV sales in the Indian context.

Recent Advances in Therapeutic Strategies to Improve Colorectal Cancer Treatment.

Colorectal cancer (CRC) is the second-leading cause of cancer-related mortality worldwide. CRC mortality results almost exclusively from metastatic disease (mCRC) for which systemic chemotherapy is often a preferred therapeutic option. Biomarker-based stratification of mCRC enables the use of precision therapy based on individual tumor mutational profiles. Activating mutations in the RAS/RAF/MAPK pathway downstream of EGFR signaling have, until recently, limited the use of EGFR-targeted therapies for mCRC; however, the development of anti-RAS and anti-RAF therapies together with improved strategies to limit compensatory signaling pathways is resulting in improved survival rates in several highly lethal mCRC sub-types (e.g., BRAF-mutant). The use of fluoropyrimidine (FP)-based chemotherapy regimens to treat mCRC continues to evolve contributing to improved long-term survival. Future advances in chemotherapy for mCRC will need to position development relative to the advances made in precision oncology.

Potential therapeutics for effort-related motivational dysfunction: assessing novel atypical dopamine transport inhibitors.

People with depression and other neuropsychiatric disorders can experience motivational dysfunctions such as fatigue and anergia, which involve reduced exertion of effort in goal-directed activity. To model effort-related motivational dysfunction, effort-based choice tasks can be used, in which rats can select between obtaining a preferred reinforcer by high exertion of effort vs. a low effort/less preferred option. Preclinical data indicate that dopamine transport (DAT) inhibitors can reverse pharmacologically-induced low-effort biases and increase selection of high-effort options in effort-based choice tasks. Although classical DAT blockers like cocaine can produce undesirable effects such as liability for misuse and psychotic reactions, not all DAT inhibitors have the same neurochemical profile. The current study characterized the effort-related effects of novel DAT inhibitors that are modafinil analogs and have a range of binding profiles and neurochemical actions (JJC8-088, JJC8-089, RDS3-094, and JJC8-091) by using two different effort-related choice behavior tasks in male Sprague-Dawley rats. JJC8-088, JJC8-089, and RDS3-094 significantly reversed the low-effort bias induced by the VMAT-2 inhibitor tetrabenazine, increasing selection of high-effort fixed ratio 5 lever pressing vs. chow intake. In addition, JJC8-089 reversed the effects of tetrabenazine in female rats. JJC8-088 and JJC8-089 also increased selection of high-effort progressive ratio responding in a choice task. However, JJC8-091 failed to produce these outcomes, potentially due to its unique pharmacological profile (i.e., binding to an occluded conformation of DAT). Assessment of a broad range of DAT inhibitors with different neurochemical characteristics may lead to the identification of compounds that are useful for treating motivational dysfunction in humans.

Management of floating hip injury: a review of the literature.

The aim of this study was to provide a comprehensive overview of floating hip injury and attempt to provide a management algorithm. PubMed was searched using the terms 'Floating hip' or 'acetabular fracture' and 'Ipsilateral femoral fracture' or 'pelvic fracture' and 'Ipsilateral femoral fracture'. One author performed a preliminary review of the abstracts and references of the retrieved articles. The mean injury severe score reported was higher than 20. Chest and abdominal injuries, as well as fractures at other sites, were the most common associated injuries. Despite the high disability rate, surgery remained the preferred option for managing these injuries. The surgical timing varied from a few hours to several days and was subjected to the principles of damage control orthopedics. Although, in most cases, fixation of femoral fractures took precedence over pelvic or acetabular fractures, there was still a need to consider the impact of damage control orthopedics, associated injuries, and surgeon's considerations and preferences. Posttraumatic arthritis, neurological deficits, heterotopic ossification, femoral head necrosis, femoral nonunion, and limb inequality were common complications of the floating hip injury. The severity of such injuries often exceeds that of an isolated injury and often requires specialized multidisciplinary treatment. In the management of these complex cases, the complexity and severity of the injury should be fully assessed, and an appropriate surgical plan should be developed to perform definitive surgery as early as possible, with attention to prevention of complications during the perioperative period.

An Evaluation of Carbon Nanotube-based and Activated Carbon-based Nanocomposites for Fluoride and Other Pollutant Removal from Water: A Review

Abstract: Water is the most critical component of the earth's ecosystem because it is fundamental to the survival of plants and animals. However, our water supply is continuously polluting. Removing contaminants from water is a crucial part of addressing water scarcity and maintaining a healthy ecosystem for all. This review focuses on adsorption and the CNTs/AC family nano adsorbents and their contribution to the removal of fluoride and other contaminants. Many types of wastewater treatment methods have been employed, including precipitation, ion-exchange, adsorption, membrane filtration, etc. A water technology with great efficiency and low cost, without requiring costly infrastructure, is the most preferred option due to adsorption. Recently, the application of carbon family nanomaterials as adsorbents has been prevalent due to their phenomenal surface properties, simple customization, immense specific surface area, numerous variations in structural type, chemical stability, porosity, low density, ease of regeneration, and the ability to be reused. Hazardous contaminants, such as fluoride, generate major public health risks. Water contamination by heavy metals provides a significant health concern, including an increased chance of getting diseases like cancer, anaemia, carcinogenic effects, and acute effects in children. The increased presence of fluoride in water could cause fluorosis, joint pain, severe anaemia, and other problems. The following review focuses on current findings regarding the utilisation of CNTs and AC nanoparticles in the elimination of harmful contaminants and fluoride.

Practice Patterns for Managing Recurrent Glioblastoma Multiforme

Abstract Introduction Glioblastoma multiforme (GBM) is a devastating form of cancer with a poor prognosis despite available treatments. Managing recurrent GBM remains challenging and lacks guidelines. This study aims to provide practice patterns for managing recurrent GBMs in India. Methods A panel of experts was assembled to develop practice patterns using the Delphi technique. Their responses were analyzed anonymously to ensure impartiality and generate recommendations. The statements were intended to be nonbinding and focused on promoting best practices in the field, without legal or regulatory authority. Results A total of 23 experts participated in the study, providing their opinions on various aspects of managing recurrent GBM. Consensus was achieved on individualized and multidisciplinary management as the preferred approach. Surgery in combination with other treatments was found to impact survival in patients older than 65 years, with re-surgery and adjuvant radiation and chemotherapy being the preferred options. Gadolinium-enhanced magnetic resonance imaging (MRI) brain with spectroscopy and diffusion-weighted imaging was favored. Molecular profiling was considered significant, with O6-methylguanine DNA methyltransferase methylation being most relevant. Surgery was recommended for recurrent GBMs, primarily based on Karnofsky's performance score (KPS). Surgical adjuncts such as neuronavigation and intraoperative MRI were considered valuable. Radiation therapy, specifically stereotactic radiosurgery, was recommended for selected cases, while opinions on re-chemotherapy were divided. Palliative care was deemed important. Conclusion This study presents practice patterns for managing recurrent GBM in India, providing standardized recommendations for practice. By implementing these, clinicians can make informed decisions, leading to improved patient outcomes and reduced variability in the management of recurrent GBM.

A Rare Cause of Gastrointestinal Bleeding in a Kidney-Pancreas Transplant Recipient – Case Report

Kidney-pancreas transplantation is the preferable therapeutic option for patients with type 1 diabetes mellitus and end-stage kidney disease. We describe the case of a 35-year-old pancreas-kidney transplant recipient with dual-graft failure that presents with massive hematochezia and hemodynamic instability, evolving into hemorrhagic shock. The diagnostic assessment revealed a fistula between a pseudoaneurysm of the right common iliac artery and the adjacent transplanted duodenum segment, a rare but life-threatening cause of gastrointestinal bleeding in these patients. An endoprosthesis was placed into the iliac artery, prophylactic antibiotics were instituted, and a pancreatic transplantectomy was performed in a second procedure. This case highlights that the diagnostic workup of gastrointestinal bleeding in pancreas-kidney transplant recipients must include the possibility of arterio-enteric fistulas, which is more frequent in the presence of pancreatic graft failure, as was the case of our patient. Endovascular exclusion is the advocated treatment. Pancreatic graft transplantectomy could also be a possible approach for patients with a failed pancreas but it is highly controversial due to potential risks.

Testing three primate species' attentional biases toward preferred and unpreferred foods: Seeing red or high valued food?

Animals navigate complex environments that present both hazards and essential resources. The prioritization of perceptual information that is relevant to their next actions, such as accessing or avoiding different resources, poses a potential challenge to animals, one that can impact survival. While animals' attentional biases toward negatively valanced and threatening stimuli have been explored, parallel biases toward differently valued resources remain understudied. Here, we assessed whether three primate species (chimpanzees [Pan troglodytes], gorillas [Gorilla gorilla gorilla], and Japanese macaques [Macaca fuscata]) prioritized their attention to positively valued resources-preferred foods compared to unpreferred foods. We employed a computerized dot probe attentional bias task in which we presented participants with paired images of their preferred and unpreferred foods in randomized locations (left or right). Latencies to touch the "probe" that replaced either image revealed that all three species responded faster to the probe when it replaced the preferred option (χ²(1) = 284.50, SE² = .03, p < .001). The uniformity of the primates' responses hints that a propensity to prioritize highly preferred items is rooted in these primates' evolutionary past, one that may serve as a mechanism to rapidly detect and locate resources such as highly valued foods. Future research will help disentangle the role that color plays in these biases. (PsycInfo Database Record (c) 2024 APA, all rights reserved).