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Motor impairment due to spasticity, weakness, and insufficient selective motor control is a key feature of cerebral palsy (CP). For standing and walking, the gluteal muscles play an important role. Physical therapy represents an evidence-based treatment to promote strength and endurance but may be limited to address selective motor control. Treatment incorporating neurostimulating techniques may increase the therapeutic benefits in these situations. The aim of this case report was to evaluate the feasibility, safety and clinical effects of a customized protocol of functional repetitive neuromuscular magnetic stimulation (frNMS). This case report describes a frNMS protocol applied to the gluteal muscles in an 8-year old boy with bilateral spastic CP. The protocol combines 12 sessions of customized physiotherapeutic exercises with simultaneous electromagnetic stimulation. frNMS protocol was adhered to as planned, no relevant adverse events were observed. At day fourafter the intervention the patient reported clinical benefits and improvements of standing and walking assessed by Gross Motor Function Measure dimensions D (+5.1%) and E (+4.2%) were documented. Body sway as measured by center of pressure displacement during posturography decreased. Clinical studies are warranted to assess effects of frNMS and its mechanisms of action in a controlled setting. [ABSTRACT FROM AUTHOR]

Motor learning interventions for children with cerebral palsy (CP) that elicit relatively permanent and transferable improvements in motor skill capability are essential. Knowledge is needed about the augmented feedback forms that most effectively promote this. This review aims to collect and analyze the current evidence for the effectiveness of different forms of feedback for motor learning in children with CP to improve motor task performance. PubMed, PsycInfo, and Cochrane Library were searched to identify relevant studies. Studies were included if (1) they were conducted in children with CP or compared children with CP to TD children and (2) a form of augmented feedback related to a motor task was administered. Initially, 401 records were identified for screening. Ultimately, 12 articles were included in the review. The evidence thus far supports the expectancy that children with CP generally benefit from feedback provided during or after performing a movement task. Due to the heterogeneity of existing studies, it is difficult to draw firm conclusions regarding relative effectiveness of feedback forms. This review showed that more high-quality research is warranted on the effectiveness of specific feedback forms on motor learning in children with CP. Children with CP benefit from several forms of knowledge of performance or knowledge of results feedback provided during or after performing a movement task. Feedback should not be provided with every performed trial. Feedback frequency can best be reduced by letting children determine after which trials they want feedback. Learning curves under similar feedback conditions varied largely between children, warranting tailor-made forms of feedback to be applied during motor learning and rehabilitation. [ABSTRACT FROM AUTHOR]

To assess attainment of individual treatment goals one year after intrathecal baclofen (ITB) pump implantation in individuals with dyskinetic cerebral palsy (CP). A multi-center prospective cohort study was conducted including 34 non-walking individuals with severe dyskinetic CP, classified as Gross Motor Function Classification System (GMFCS) IV/V, aged 4–24 years, 12 months after pump implantation. The main outcome measure was Goal Attainment Scaling (GAS). Predictors of GAS results were analyzed. Complications were registered systematically. Seventy-one percent of individuals with dyskinetic CP fully achieved one or more treatment goals. One or more treatment goals were partially achieved in 97% of individuals. Two factors were found to be associated with attainment of goals: Dyskinesia Impairment Scale (DIS) score at baseline and the difference in pain score between baseline and follow-up. These two variables explain 30% of the variance in the outcome. Intrathecal baclofen is effective in achieving individual treatment goals in children and young adults with dyskinetic CP after nine to 12 months of ITB treatment. A positive outcome on treatment goals is, for a small part, associated with higher severity of dystonia at baseline and with improvement of pain during treatment. Dutch Trial Register, number NTR3642. Intrathecal baclofen treatment is effective in attainment of personal treatment goals, one year after pump implantation in patients with dyskinetic cerebral palsy. A positive outcome on treatment goals is, for a small part, related to higher severity of dystonia at the start and on improvement of pain during treatment. [ABSTRACT FROM AUTHOR]

A small subset of cases of inflammatory bowel disease (IBD) occurs as a result of single gene defects, and typically occurs in young or very young pediatric patients, referred to as "monogenic very-early onset IBD (VEO-IBD)". The gene variants leading to monogenic VEO-IBD are often associated with primary immunodeficiency syndromes. A six year-old girl presented to our gastroenterology clinic with LRBA deficiency with a heterozygous mutation at c.1399 A > G, p Met467Val, histopathologic chronic active colitis without granulomas and clinical chronic colitis. Her gastrointestinal symptoms began at age 5 with bloody diarrhea, abdominal pain and weight loss. Whole exome sequencing revealed a CARD11 heterozygous de novo mutation (c.220 + 1G > A). She was in clinical remission on only abatacept. We present a case of monogenic VEO-IBD associated with two heterozygous variants in LRBA1 and CARD11, both considered as key players in the newly proposed "immune TOR-opathies". [ABSTRACT FROM AUTHOR]

Numerous discovered and undiscovered near-Earth objects (NEOs), celestial bodies from outer space with diverse physical properties, have ensued major potential impact threats to the Earth. For a timely and accurate response in monitoring NEOs entering Earth's orbit, the future applied Moon-based monitoring platform (MBMP) will fully utilize the vast flat Moon's surface, along with low thermal noise in the prospective permanent shadow area, low gravity and vacuum environment, and special space relation, among other advantages over the established ground-based monitoring platform (GBMP) and space-based monitoring platform (SBMP). Future single or clustered platforms might indeed survey space with limited solar influence involved. Through downloaded data from the Center for Near Earth Object Studies, this study analysed MBMP performance and studied the commonly visible ratio (VR) based on the overall geometry of Sun–Moon–Earth and NEOs. Results from the average near-side MBMP VR outperformed the far side GBMP, and other satellites even by 0.4. This provides locations with a high probability for monitoring platforms among the downloaded NEOs, while the rest of the Moon's surface can serve as crucial underlying support for timely NEO monitoring and a valuable complement for GBMP and SBMP. [ABSTRACT FROM AUTHOR]

Fatigue is a common problem for adults with cerebral palsy (CP) and may be related to the decline in physical function, including the loss of the ability to walk. To estimate the overall prevalence of fatigue in adolescents and adults with cerebral palsy. MEDLINE (OVID), EMBASE (OVID), CINAHL, PsycINFO, and Web of Science electronic databases were searched in September 2021. The review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO), registration CRD42021275596. Two authors independently screened studies according to Preferred Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and the methodological quality of included studies was assessed using the Joanna Briggs Institute (JBI) Prevalence Critical Appraisal Checklist. Of the 1022 studies identified, fifteen met the inclusion criteria. Study quality assessment was performed using the Joanna Briggs Institute (JBI) Prevalence Critical Appraisal Checklist, with scores ranging from 4 out of 10 to 10 out of 10. Pooled prevalence estimates for twelve studies were 52.9% (95% confidence interval [CI]40.9–64.6). Fatigue was higher in people with bilateral CP than unilateral CP, and higher in people classified as Gross Motor Function Classification System (GMFCS) levels III-V. More than half of the adults with CP (52.9%) reported living with fatigue. Adults with CP frequently reported fatigue that may lead to activity limitations and/or restrictions. Fatigue was strongly correlated with pain, depression, and reduced quality of life. Assessment and appropriate fatigue management techniques are necessary to enhance capacity for everyday functioning and quality of life. [ABSTRACT FROM AUTHOR]

To describe the prevalence of bladder and bowel dysfunction (BBD) in 8–10-year-old children with cerebral palsy and its association with motor, cognitive, and autonomic dysfunction. A cross-sectional, random sample study of parents of 8–10-year-old children with cerebral palsy. Tools: The Enuresis/Urinary Incontinence Parental Questionnaire, the Functional Independence Measure children's version, the autonomic signs questionnaire, and the Gross Motor Function Classification System. 39 out of 59 parents consented to participate, whereas 25.64% reported complete continence. Of the 29 children with BBD, 21 (72.4%) had lower urinary tract symptoms and bowel problems. Only two of the children received conservative and noninvasive treatments. Lastly, motor, cognitive and autonomic impairments were associated with incontinence. BBD is common in 8–10-year-old children with cerebral palsy at all levels of functioning. Most having both lower urinary tract symptoms and bowel problems. [ABSTRACT FROM AUTHOR]

In children with cerebral palsy (CP), with impaired trunk control and toe-walking, trunk-focused rehabilitation (TFR) based on postural activities was hypothesized to improve trunk postural control, early trunk deceleration, and ankle dorsiflexion braking during walking. Methods: Seventeen children with CP (5–12 years) walking autonomously were randomly assigned to TFR and then usual rehabilitation (TFR-UR) or vice versa (UR-TFR). Only after TFR was significant improvements in (i) the Trunk Control Measurement Scale score, postural sway on an unstable sitting device and standing, and (ii) early sternal and sacral decelerations and coupled negative ankle power due to plantar flexors. TFR improves trunk dynamics and consequently improves coupled toe-walking. [ABSTRACT FROM AUTHOR]

Menstrual health and genital hygiene behavior in patients with cerebral palsy (CP) is underrecognized, undertreated, and negatively affects quality of life. The aim of this case-control study is to compare menstrual health and genital hygiene behaviors in adolescent girls and young women with CP to a healthy women control group. Participants were invited to study via social media tools between August 2021 and February 2022. The study included 74 adolescent girls and young women with CP and 89 healthy women. Menstrual status with semi-structured questions, menstrual symptoms with "Menstrual Symptom Questionnaire (MSQ)," genital hygiene behavior with "Genital Hygiene Behavior Scale (GHBS)" were evaluated. The control group scored significantly higher on the MSQ sub-dimensions of "negative effects somatic complaints" (r = 0.396; p <.001), "menstrual pain" (r = 0.287; p <.001), "coping methods" (r = 0.291; p <.001), and total score (r = 0.395; p <.001), as well as the GHBS sub-dimensions of "awareness of abnormal findings" (r = 0.270; p =.001) and "menstrual hygiene" (r = 0.495; p <.001) and total score (r = 0.393; p <.001). People with CP had worse genital hygiene behavior, had less menstrual symptoms, and behaved differently about the menstruation symptoms. This study focused on adolescent girls and young women with CP who cannot easily express their own experiences and concerns, emphasized that their needs should be identified by determining their menstrual health and genital hygiene behaviors. Clinical Registration Name, Registration Number, Registration Date: Menstrual Health and Genital Hygiene Status in Cerebral Palsy and NCT04985045, August 2,2021. [ABSTRACT FROM AUTHOR]

Functional mobility in children with cerebral palsy (CP) varies widely and is affected by many factors related to the child and environment. Understanding this variability in child's natural environments: home, school, and community; and its determinants are important for effective child management. This cross-sectional study aims to investigate the functional mobility of children with CP within home, school, and community, and explore its determinants. Participants were 107 children with CP (aged 6.4 ± 2.9 years). Functional Mobility Scale was the outcome variable. Potential determinants included child-associated impairments and interventions. Three ordinal logistic regression analyses were conducted. Children in Gross Motor Functional Classification System-Expanded and Revised level I walked without assistive devices in all environments, while children in levels II/III used different mobility methods in different environments. Children in levels IV/V used a wheelchair or had no form of functional mobility in all environments. Determinants of mobility varied across different environments but included impairments (visual impairments, scoliosis) and interventions (Botox, medications for spasticity, orthoses). Child impairments and interventions received should be considered when exploring mobility options for children with CP in different environments. Further research is needed to examine other environmental and personal factors affecting mobility. [ABSTRACT FROM AUTHOR]

The intestinal epithelial barrier is susceptible to injury from insults, such as ischemia or infectious disease. The epithelium's ability to repair wounded regions is critical to maintaining barrier integrity. Mechanisms of intestinal epithelial repair can be studied with models that recapitulate the in vivo environment. This review focuses on in vitro injury models and intestinal cell lines utilized in such systems. The formation of artificial wounds in a controlled environment allows for the exploration of reparative physiology in cell lines modeling diverse aspects of intestinal physiology. Specifically, the use of intestinal cell lines, IPEC-J2, Caco-2, T-84, HT-29, and IEC-6, to model intestinal epithelium is discussed. Understanding the unique systems available for creating intestinal injury and the differences in monolayers used for in vitro work is essential for designing studies that properly capture relevant physiology for the study of intestinal wound repair. [ABSTRACT FROM AUTHOR]

Using the 2019 National Child Abuse and Neglect Data System, the prevalence and predictors of substantiated reports of child sex trafficking (CST) (n = 1,286) and other maltreatment (n = 705,778) (e.g., physical abuse, sexual abuse, but not sex trafficking) were explored. Descriptive statistics were used to present the profile of children who were victims of CST, and negative binomial regression modeling explored the individual/ontological-, microsystem-, and exosystem-level risk factors for CST compared to other forms of maltreatment. Findings showed that multiracial identity, substance use, disability status; caregiver type—most notably living in a group home—and residing in more rural areas; and professionals as the reporting source were associated with CST versus other maltreatment. Implications for research, policy, and practice for CST are discussed. [ABSTRACT FROM AUTHOR]

In this article, the author reflects on the unsolved cause of systemic lupus erythematosus while also criticizing the new age molecular biology. He states that by a novel self-organized criticality theory of autoimmunity, the cause of SLE was recognized to be the repeated immunization with omnipresent antigens. An overview of the reaction of T cells on immunization of antigen is offered. He also suggests that the answer to autoimmunity is the generation of aiCD4 T cells.

Mucus secretion from colonic goblet cells is an important host defense mechanism against the harsh lumenal environment. Yet how mucus secretion is regulated is not well understood. We discovered that constitutive activation of macroautophagy/autophagy via BECN1 (beclin 1) relieves endoplasmic reticulum (ER) stress in goblet cells, which in turn produce a thicker and less penetrable mucus barrier. Pharmacological reduction of the ER stress or activation of the unfolded protein response (UPR) in mice, regardless of autophagy activation, lead to excess mucus secretion. This regulation of mucus secretion by ER stress is microbiota-dependent and requires the activity of the intracellular sensor NOD2 (nucleotide-binding oligomerization domain containing 2). Excess mucus production in the colon alters the gut microbiota and protects from chemical- and infection-driven inflammation. Our findings provide new insights into the mechanisms by which autophagy regulates mucus secretion and susceptibility to intestinal inflammation. Abbreviations:BECN1– Beclin 1; ER– endoplasmic reticulum; UPR – unfolded protein response; NOD2 – nucleotide-binding oligomerization domain containing 2; IBD– inflammatory bowel disease; BCL2- B cell leukemia/lymphoma 2; TUDCA- tauroursodeoxycholic acid; ATG16L1– autophagy related 16 like 1; LRRK2- leucine-rich repeat kinase 2. [ABSTRACT FROM AUTHOR]

Lys05 is a previously undescribed dimeric chloroquine which more potently accumulates in the lysosome and blocks autophagy compared with HCQ. Lys05 produced more potent antitumor activity as a single agent both in vitro and in vivo in multiple human cancer cell lines and xenograft models compared with HCQ. Initial structure-activity relationship studies demonstrated that the increased activity associated with Lys05 was due to the bivalent aminoquinoline rings, C7-Chlorine, and a short triamine linker. While lower doses of Lys05 were well tolerated and associated with antitumor activity, at the highest dose tested, Lys05 produced Paneth cell dysfunction and intestinal toxicity, similar to what can be observed in mice and humans with genetic defects in the autophagy gene ATG16L1. Lys05 is therefore a new lysosomal autophagy inhibitor that has potential to be developed further into a drug for cancer and other medical applications. [ABSTRACT FROM AUTHOR]

Triazolo-thiadiazines 4a–f and triazolo-tetrazines 8g–l were prepared from reaction of 3-(4-amino-5-mercapto-4H-1,2,4-triazol-3-yl)-2H-chromen-2-one with the respective hydrazonoyl halides 2a–f and 2g–l. Moreover, the reaction of the aminomercaptotriazole derivative with phenacyl bromide and ethyl 2-chloro-3-oxobutanoate followed by the coupling reaction of the products with benzenediazonium chloride yielded the corresponding products 4f and 8g, respectively. All of the newly prepared heterocyclic derivatives were determined using spectral data, elemental analysis, and alternate methods. The in-vivo anticonvulsant and CNS-depressant activities of all the prepared derivatives were tested using the maximal electroshock method and showed excellent activities, especially triazolo[4,3-b]tetrazine derivatives 8j, 8k, and 8l. Additionally, their structure–activity relationship was proven clearly, demonstrating that electron-releasing groups increase activities while electron-withdrawing groups lower them. [ABSTRACT FROM AUTHOR]

Alkyl/aralkyl/phenacyl thiotriazolyl isoindoline-1,3-diones were synthesized by the reaction of dipotassium cyanodithioimidocarbonate salt with hydrazine hydrate, phthalic anhydride and alkyl/aralkyl/phenacyl bromides using acetic acid and sodium acetate via a one-pot four-component synthesis. Alternatively, the same final products were also synthesized by the reaction of dipotassium cyanodithioimidocarbonate salt with hydrazine hydrate in presence of acetic acid to give intermediate 5-amino-4H-1,2,4-triazole-3-thiol [I]. This compound was further reacted with phthalic anhydride, followed by a reaction with alkyl/aralkyl/phenacyl bromides to give the title compounds in a two-step process. In this method, the yields are less compared to one-pot four-component synthesis. All the newly synthesized compounds were characterized by their spectral studies (FTIR, 1H-NMR, 13C-NMR, Mass). Further, the synthesized compounds were screened for their in-vitro anticancer activity. Compounds 5 m, 5p, 5r showed good cytotoxic assay against Hela cancer cell lines. Furthermore, compounds 5(a-t) were subjected to their docking analysis and DFT calculations. [ABSTRACT FROM AUTHOR]

In light of the potential applications as full-colour organic emitting materials crossing the entire visible spectra, the novel diphenylamino submitted 2-(2'-hydroxyphenyl) benzothiazole derivative 2-(benzo[d]thiazol-2-yl)-4-(9H-diphenylamino-9-yl)phenol (pPhOH) is explored in this work about its excited state behaviours. Solvent-polarity-related photo-induced hydrogen bonding effects of pPhOH indicate nonpolar aprotic solvents largely enhance S1-state hydrogen bonding interactions. Charge reorganisation stemming from photoexcitation and polarity-dependent energy gap between HOMO and LUMO orbitals further reveals the excited state intramolecular proton transfer (ESIPT) tendency. Insights into potential energy curves (PECs) along ESIPT paths in solvents with different polarities and electronic spectral behaviours of pPhOH as well as its proton-transfer tautomer pPhOH-T, we present solvent polarity could harness the excited state behaviours for pPhOH system. [ABSTRACT FROM AUTHOR]

Using survey data collected from Hubei province, China's Covid-19 epicentre, in August 2020, this study examines how fertility intentions of Chinese citizens changed during the Covid-19 pandemic. We consider not only whether people changed their fertility plans due to Covid-19 but also distinguish three types of change: bringing forward ('sooner'), postponing ('later'), and abandoning ('never') planned fertility. Over half of those who planned to have a child intended to change their fertility plans due to Covid-19. Younger individuals, those of non-Han ethnicities, urban residents, those with one child already, and those with ever-infected family members were more likely to change their fertility plans. While the effects of some characteristics seem to be short term, other characteristics such as age and number of children show more consequential influences. Older individuals and those planning their second child were particularly prone to abandoning their childbearing plans due to Covid-19. The pandemic may thus complicate China's latest efforts to boost its low fertility. [ABSTRACT FROM AUTHOR]

T helper 17 (Th17) cells are IL-17-producing CD4 T cells that play a crucial role in autoimmune diseases. IL-17 is a key cytokine for host protection against mucosal and skin infection but is also one of the major pathogenic cytokines. IL-1 and IL-23 are requisite for stimulating pathogenic Th17 cell differentiation and proliferation. Therapeutics targeting the IL-17/IL-23 pathway are widely used clinically for the treatment of autoimmune diseases. Besides IL-17, pathogenic Th17 cells produce granulocyte-macrophage colony-stimulating factor, tumor necrosis factor α, interferon γ, IL-21 and IL-22. However, Th17-targeted therapy has not yet been established. T cell metabolism orchestrates T cell survival, cell differentiation, epigenetic change and function and each T cell subset favors a particular metabolic pathway. Recent studies have provided novel insights into the role of T cell metabolism in the pathogenesis of autoimmune diseases. The current review focuses on the role of Th17 cell metabolism in autoimmune diseases, particularly glycolysis, amino acid metabolism, lipid metabolism, as well as the regulators of these processes, including mTORC1. Therapeutics targeting T cell metabolism in autoimmune diseases could serve as a possible treatment option for patients who are refractory to or unresponsive to conventional therapy. [ABSTRACT FROM AUTHOR]

A theoretical and experimental approach for a series of synthetic aromatic organic compounds as salicylaldehyde thiosemicarbazones were prepared from 4,4-dimethyl-3-thiosemicarbazide and substituted salicylaldehydes. The newly synthesized compounds were fully characterized by FT-IR, UV-vis, 1H-NMR, 13C-NMR, CHNS, HRMS, and fluorescence spectroscopy. DFT calculations were performed on the compounds to get a structure-property relationship. Some global reactivity descriptors like chemical potential (μ), electronegativity (χ), hardness (η), and electrophilicity index (ω) were also evaluated using DFT method. Optical nonlinearity response of our novel compounds was also studied which may be significant for the hi-tech NLO applications. These compounds were also evaluated for their antibacterial activities against certain strains of Gram-positive and Gram-negative bacteria. They displayed moderate activity against using bacterial strains. Additionally, inspiring from recent developments to find a potential inhibitor for COVID-19 virus, molecular docking calculations were also performed on studied compounds to see if our novel compounds show affinity for main protease (Mpro) of SARS-CoV-2 (PDB ID: 6LU7). We have found stable docked structures where docked compounds could readily bound to the SARS-CoV-2, which would be lethal to main protease (Mpro). The molecular docking calculations of the present compounds into the protease of SARS-CoV-2 virus revealed the binding energy in the range of −7.86 to 9.92 kcal/mol with inhibition constant values in the range of 1.360–5.820 µM. These binding affinities are reasonably well as compared to recently docking results of anti-SARS-CoV-2 drugs like chloroquine (−6.293 kcal/mol), hydroxychloroquine (−5.573 kcal/mol) and remdesivir (−6.352 kcal/mol) when targeted to the active-site of SARS-CoV-2 main protease (Mpro). [ABSTRACT FROM AUTHOR]

Cholera was the emblematic disease of the nineteenth-century Europe. This article explores the cultural ramifications of cholera by concentrating on the ways in which public discourse participated in circulating information on the disease. It focuses on the reuse of texts about cholera in the Finnish press from 1860 to 1920. The most difficult cholera epidemics in Finland were the first ones in the 1830s and 1850s, and the number of casualties dropped significantly towards the end of the century. At the same time, however, cholera was discussed more than ever, and there was the rising curve of the references to cholera from the 1860s onwards. In Finland, the public discourse on cholera was also entangled with the rising nationalism towards the end of the nineteenth century. [ABSTRACT FROM AUTHOR]

Cells activate protective mechanisms to overcome stressful conditions that threaten cellular homeostasis, including imbalances in calcium, redox, and nutrient levels. Endoplasmic reticulum (ER) stress activates an intracellular signaling pathway, known as the unfolded protein response (UPR), to mitigate such circumstances and protect cells. Although ER stress is sometimes a negative regulator of autophagy, UPR induced by ER stress typically activates autophagy, a self-degradative pathway that further supports its cytoprotective role. Sustained activation of ER stress and autophagy is known to trigger cell death and is considered a therapeutic target for certain diseases. However, ER stress-induced autophagy can also lead to treatment resistance in cancer and exacerbation of certain diseases. Since the ER stress response and autophagy affect each other, and the degree of their activation is closely related to various diseases, understanding their relationship is very important. In this review, we summarize the current understanding of two fundamental cellular stress responses, the ER stress response and autophagy, and their crosstalk under pathological conditions to help develop therapies for inflammatory diseases, neurodegenerative disorders, and cancer. [ABSTRACT FROM AUTHOR]

Neuroendocrine prostate cancer (NEPC) is an aggressive form of prostate cancer frequently seen after prolonged treatment of castration resistant prostate cancer (CRPC). NEPC has become increasingly prevalent over the last 20 years, with a poor prognosis caused by a late diagnosis and limited treatment options. Recent advances in PET/CT imaging and targeted radioimmunotherapy are promising, but more research into additional treatment options is needed. The aim of this review is to analyze the current imaging and treatment options for NEPC, and to highlight future potential treatment strategies. A Pubmed search for 'Neuroendocrine Prostate Cancer' was performed and relevant articles were reviewed. The recent FDA approval and success of 177 PSMA Lutetium in CRPC is promising, as 177 Lutetium could potentially be paired with a NEPC specific biomarker for targeted therapy. Recent laboratory studies pairing DLL3, which is overexpressed in NEPC, with 177 Lutetium and new PET agents have showed good efficacy in identifying and treating NEPC. The success of future development of NEPC therapies may depend on the availability of 177 Lutetium, as current supplies are limited. Further research into additional imaging and treatment options for NEPC is warranted. Neuroendocrine prostate cancer (NEPC) is a rare form of prostate cancer. People with NEPC have typically had previous treatment for prostate cancer. NEPC is usually found after prostate cancer cells have spread outside of the prostate. NEPC may not produce typical prostate cancer markers such as prostate specific antigen (PSA). This can make detection of NEPC difficult. NEPC is difficult to treat because NEPC does not respond very well to typical prostate cancer medications. Because of this, people with NEPC typically have a shortened survival. Many researchers have been developing new ways to find and treat NEPC. New methods of imaging with PET/CT scans are better at detecting NEPC than standard imaging. Treatments that specifically target NEPC cells are currently being researched, but these treatments have not been used on any patients yet. This article describes these research efforts and recommends that more research should be done to find treatments for NEPC. [ABSTRACT FROM AUTHOR]

This study discusses whether olfactomedin 4 (OLFM4) could be used as a sensitive and specific biomarker in the early diagnosis of gastric cancer (GC) after gastric intestinal metaplasia (GIM). An integrative analysis combining data derived from the Gene Expression Omnibus (GEO) and cBioPortal databases was performed to investigate the potential molecular biomarker. Immunohistochemistry and quantitative real-time polymerase chain reactions were used to measure the expression of messenger ribonucleic acid (mRNA) and protein by OLFM4. In combination with the gastroscopic findings and the OLFM4 expression in GIM-GC, a predictive model was established. The receiver operator characteristic curve (ROC) was applied to assess the diagnostic value of the model for GIM-GC. According to the GEO and cBioPortal databases, OLFM4 was identified as a key gene in the diagnosis of GIM-GC. Higher protein expression of OLFM4 was found in GIM and GIM-GC compared with chronic superficial gastritis (GS) (p < 0.05). The positive expression rate of OLFM4 in paracancerous tissue (GCP) was higher than in GIM (p > 0.05). There was no significant difference between GIM-GC and GCP (p > 0.05). The mRNA expression of OLFM4 was similar to the protein expression, and the positive expression rate was higher in early GIM-GC than in GIM (p < 0.05). Olfactomedin 4 could be used as a biomarker for the early diagnosis of GIM-GC, and the logistic predictive model could be an effective tool for increasing the early diagnostic rate. [ABSTRACT FROM AUTHOR]

This study presented the Turkish translation of the Early Activity Scale for Endurance (T-EASE) which was developed to evaluate the endurance for physical activity of preschool children with Cerebral Palsy (CP), and its validity and reliability. Fifty-five children with CP aged between 2 and 5 years were included in the study. The Gross Motor Function Classification Scale (GMFCS) and Pediatric Outcomes Data Collection Instrument (PODCI) were used to determine motor function levels and quality of life of the study population. The T-EASE had good test-retest reliability (ICC = 0.996), internal consistency (α = 0.903), higher construct validity approved by confirmatory factor analysis, and criterion validity supported by the weak-to-strong correlations between T-EASE and GMFCS, and PODCI. The T-EASE scores were significantly different between GMFCS levels (p <.05). The T-EASE was found to be valid and reliable to determine the endurance for physical activity of Turkish pre-school children with CP with the sensitivity to changes in motor function levels. [ABSTRACT FROM AUTHOR]

The current study aimed to investigate developmental functioning in infants and toddlers with autism spectrum disorder (ASD), seizures, cerebral palsy (CP), and atypical development. An ANOVA was utilized to investigate the differences between neurodevelopmental group on BDI-2 developmental quotient and a MANOVA was used to investigate the differences between the groups and five developmental domains. The results indicated statistically significant differences in overall developmental functioning and each subdomain of the BDI-2. These findings provide the basis for further research to investigate comorbidities of the three neurodevelopmental disorders and parse out the impact of intellectual disability (ID). [ABSTRACT FROM AUTHOR]

To map research conducted with adults with cerebral palsy (CP) to the International Classification of Functioning, Disability and Health (ICF) to understand the array of research available, identify key clinical messages and inform future research. An overview of systematic reviews was conducted. Comprehensive searches (to December 2021) were conducted in PsycINFO, Web of Science, MEDLINE, CINAHL, Cochrane, JBI, and EMBASE. Eligible studies were systematic reviews that included primary studies of adults with CP. Included reviews were assessed for study quality and mapped to the ICF components and chapters. A narrative synthesis of commonly reported outcomes within the component/s and chapter/s was conducted. All 24 included reviews were published since 2010. Thirteen focused on body functions: movement related functions and cardiovascular and respiratory systems. Although nine reviews focused on gait and mobility, considerable overlap of included studies limited the volume of evidence and variability in review quality limited generalisability of findings. Research involving adults with CP is growing; however, this overview of reviews found a predominant focus on mobility and gait. Future research, informed by consumer priorities, is needed to address a broader range of key health and participation outcomes. Fitness, mobility, and gait were the most common research topics found in these systematic reviews suggesting a narrow research focus in adults with CP. There are significant gaps in our knowledge to inform clinical messages for practice about broad long-term outcomes of CP and how best to support their activity performance and participation. There is very limited evidence with which to guide and support rehabilitation professionals working in this field. [ABSTRACT FROM AUTHOR]

A series of novel indolo[3,2-c]isoquinoline hybrids derivatives were synthesized. On the basis of spectroscopic and analytical data, the structures of newly synthesized compounds were determined. They were further evaluated for their in vitro antimicrobial, antioxidant anticancer and anti-TB activities. Results reveal that compounds 4a and 5a displayed better potency against all bacterial strains and compound 3b showed significant antifungal action against all fungi tested. Compound 4b display excellent antioxidant capability. Compounds 3a, 4a, and 5a bearing chloro on indolo[3,2-c]isoquinoline ring were found have higher potency against all cancer cell lines. Compound 5b displayed potent antitubercular activity against Mycobacterium tuberculosis H37Rv strain with MIC 0.12 μg/mL. Consequently, a five-point e-pharmacophore model (AADDR) was built. Docking studies displayed that compounds 2a, 2b, 3a, 4b, and 4c exhibited stronger interactions and higher binding affinity toward Glu166, Gln189, and His41, which are critical amino acid residues that play a significant role in PDB: 7D1M (SARS-CoV-2 Mpro) through hydrogen bonding, hydrophobic and π-π interactions. Further, frontier molecular orbitals studies were executed to understand their orbital energies and HOMO-LUMO lowest energy gap is 8.39 eV shown by compound 5a. [ABSTRACT FROM AUTHOR]

Oral administration is the preferred route for drug administration that leads to better therapy compliance. The intestine plays a key role in the absorption and metabolism of oral drugs, therefore, new intestinal models are being continuously proposed, which contribute to the study of intestinal physiology, drug screening, drug side effects, and drug–drug interactions. Advances in pharmaceutical processes have produced more drug formulations, causing challenges for intestinal models. To adapt to the rapid evolution of pharmaceuticals, more intestinal models have been created. However, because of the complexity of the intestine, few models can take all aspects of the intestine into account, and some functions must be sacrificed to investigate other areas. Therefore, investigators need to choose appropriate models according to the experimental stage and other requirements to obtain the desired results. To help researchers achieve this goal, this review summarised the advantages and disadvantages of current commonly used intestinal models and discusses possible future directions, providing a better understanding of intestinal models. [ABSTRACT FROM AUTHOR]