Rejected

Substance use disorder (SUD) is a chronic, relapsing disease with a highly multifaceted pathology that includes (but is not limited to) sensitivity to drug-associated cues, negative affect, and motivation to maintain drug consumption. SUDs are highly prevalent, with 35 million people meeting criteria for SUD. While drug use and addiction are highly studied, most investigations of SUDs examine drug use in isolation, rather than in the more prevalent context of comorbid substance histories. Indeed, 11.3% of individuals diagnosed with a SUD have concurrent alcohol and illicit drug use disorders. Furthermore, having a SUD with one substance increases susceptibility to developing dependence on additional substances. For example, the increased risk of developing heroin dependence is twofold for alcohol misusers, threefold for cannabis users, 15-fold for cocaine users, and 40-fold for prescription misusers. Given the prevalence and risk associated with polysubstance use and current public health crises, examining these disorders through the lens of co-use is essential for translatability and improved treatment efficacy. The escalating economic and social costs and continued rise in drug use has spurred interest in developing preclinical models that effectively model this phenomenon. Here, we review the current state of the field in understanding the behavioral and neural circuitry in the context of co-use with common pairings of alcohol, nicotine, cannabis, and other addictive substances. Moreover, we outline key considerations when developing polysubstance models, including challenges to developing preclinical models to provide insights and improve treatment outcomes.

We report a case of a middle-aged woman who developed hypertensive retinopathy following oral administration of Anlotinib.

Although regulatory T cells (Tregs) play crucial roles in the maintenance of immune hemostasis, the numbers of peripheral Tregs in patients with psoriatic arthritis (PsA) remain unclear. We measured these numbers and the efficacy and safety of low-dose interleukin-2 (IL-2) therapy.

A woman in her thirties developed complex regional pain syndrome in her left shoulder due to a traffic accident. She demonstrated autonomic nervous symptoms (swelling, sweating, and skin color asymmetry) in her left hand, severe allodynia, neglect-like symptoms (NLS), impaired body image associated with impaired body awareness, and functional impairment of the left shoulder and elbow. She also reported physical self-disgust toward her affected limb, describing it as "reptilian," as well as aversion to touching others; this body awareness exacerbated her pain and NLS. We therefore conducted stepwise interventions using body shadows. The intervention did not trigger physical self-disgust, enabling formation of body ownership and a body image unaccompanied by pain. Consequently, the patient showed improvements in pain, NLS, and autonomic nervous symptoms.

This study aimed at investigating the anti-inflammatory potential of essential oil from rhizome and leaf of Rosc. (ACEO) with the focus of its topical anti-inflammatory activity along with its dominant compounds 1,8-cineole and -terpineol using mouse ear edema model. ACEOs were analyzed by GC-MS. The anti-inflammatory activity was determined by studying the inhibition of overproduction of proinflammatory mediators-nitric oxide, reactive oxygen species, prostaglandins, cyclooxygenases, and cytokines induced by lipopolysaccharides in murine macrophages. Topical anti-inflammatory and antinociceptive activity was studied by 12-O-tetradecanoylphorbol-13-acetate (TPA) induced skin inflammation and formalin-induced pain model in mice, respectively. Rhizome oil has 1,8-cineole (31.08%), -terpineol (10.31%), and fenchyl acetate (10.73%) as major compounds whereas the ACEO from leaves has 1,8-cineole (38.45%), -terpineol (11.62%), and camphor (10%). ACEOs reduced the production of inflammatory mediators in a concentration-dependent manner. Further, ACEO and its major compounds reduced ear thickness, weight, myeloperoxidase, and cytokines significantly ( < 0.01) in mouse ear. Dose-dependent reduction in flinching and licking in both the phases of pain sensation concludes the topical analgesic effect. Our findings suggest the potency of topical use of ACEOs for inflammatory disease conditions.

The aim: To study clinical efficiency of using the diode laser in the treatment of chronic catarrhal and hypertrophic gingivitis.

Brain radiotherapy is the standard treatment option for multiple brain metastases (BMs) from non-small cell lung cancer (NSCLC), especially in the absence of a driver mutation. However, the prognosis for such patients remains poor. Apatinib is a potent antiangiogenic compound directed at the vascular endothelial growth factor receptor-2 (VEGFR-2); however, to date, there are no investigations of apatinib concurrent with brain radiotherapy for NSCLC patients with BMs. We report a case of EGFR wild-type and ALK-negative lung adenocarcinoma patient with multiple symptomatic BMs, who received apatinib together with brain radiation therapy. A favorable oncologic outcome was achieved for both brain metastatic lesions and the primary pulmonary tumor. A 61-year-old female (never smoker) who initially presented with headache and dizziness was diagnosed with lung adenocarcinoma with multiple brain metastasis (cT2aN3M1b stage IV), and was negative for EGFR and ALK. The patient refused to receive chemotherapy and was only amenable to brain radiotherapy and targeted therapy. After approval from the institutional ethics committee, she underwent concurrent oral apatinib (500 mg/day) with whole brain radiation therapy (WBRT) (37.5Gy) with simultaneous in-field boost (49.5Gy) in 15 fractions with image guided intensity-modulated radiotherapy. Three weeks later, neurologic symptoms entirely ceased and a partial response (PR) for the BMs with near-complete resolution of peritumoral brain edema was achieved. Chest CT performed at the same time and showed shrinkage of the lung primary with a PR. The patient suffered grade III oral mucositis one week after brain radiotherapy and refused further apatinib. At 12 months after brain radiotherapy, the brain tumors remained well controlled. This is the first known documentation of a rapid clinical response of apatinib concurrent with brain radiotherapy in a lung adenocarcinoma patient with symptomatic multiple BMs. Apatinib combined with brain radiotherapy could be an alternative treatment option for BMs from NSCLC, especially for those without a driver mutation. Further clinical trials are required to corroborate this discovery.

A 33-year-old gravid female from Pakistan presented to the Emergency Department with persistent, intractable low back pain and neuropathic left L5 leg pain, associated with a left foot drop. There was a notable history of weight loss for 1 year. Investigations revealed a large collection in the right posterior paraspinal muscles tracking from a large bony defect in the right half of her sacrum extending into the pelvis. The collection was suggestive of an abscess and underwent US-guided aspiration. Culture, PCR examination, and bone biopsy were culture-negative for tuberculosis (TB). Samples taken from the placenta showed two small granulomata in the chorionic villi only. A multidisciplinary approach commenced with initiation of empirical TB treatment and attempted normal vaginal delivery. An urgent caesarean section for the delivery of the baby was required for failure to proceed. Spinal-pelvic stabilization in two stages was performed for the unstable fracture pattern, followed by pharmacotherapy and physiotherapy rehabilitation. At 12-month follow-up, the patient showed resolving TB and eradication of the paraspinal abscess. There was bony union and stability of the spinal-pelvic reconstruction. Back pain and sciatica can be common in pregnancy. However, this case highlights a rare occurrence of culture-negative extrapulmonary TB leading to an unstable spinal-pelvic fracture requiring a multidisciplinary approach for careful obstetric and orthopaedic treatment with empirical treatment by the infectious disease team and microbiology.

Sepsis is defined as dysregulated host response caused by systemic infection, leading to organ failure. It is a life-threatening condition, often requiring admission to an intensive care unit (ICU). The causative agents and processes involved are multifactorial but are characterized by an overarching inflammatory response, sharing elements in common with severe inflammatory response syndrome (SIRS) of non-infectious origin. Sepsis presents with a range of pathophysiological and genetic features which make clinical differentiation from SIRS very challenging. This may reflect a poor understanding of the key gene inter-activities and/or pathway associations underlying these disease processes. Improved understanding is critical for early differential recognition of sepsis and SIRS and to improve patient management and clinical outcomes. Judicious selection of gene biomarkers suitable for development of diagnostic tests/testing could make differentiation of sepsis and SIRS feasible. Here we describe a methodologic framework for the identification and validation of biomarkers in SIRS, sepsis and septic shock patients, using a 2-tier gene screening, artificial neural network (ANN) data mining technique, using previously published gene expression datasets. Eight key hub markers have been identified which may delineate distinct, core disease processes and which show potential for informing underlying immunological and pathological processes and thus patient stratification and treatment. These do not show sufficient fold change differences between the different disease states to be useful as primary diagnostic biomarkers, but are instrumental in identifying candidate pathways and other associated biomarkers for further exploration.

Carbon monoxide (CO) poisoning is a common health problem among people in many countries, primarily because of its severe clinical effects and high toxicological morbidity and mortality. Acute brain injury and delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) are the most common neurological complications. This study was performed to assess the efficacy of N-butylphthalide (NBP) and dexamethasone (DXM) combined with hyperbaric oxygen (HBO) in patients with DEACMP.