Facilitators and barriers to learning faced by female students with disability in higher education.

This study was aimed to investigate the learning experiences' facilitators and barriers that is encountered by the physically disabled female students during their higher education. Twenty semi-structured interviews were conducted with female students with physical disabilities aged between 19 and 33 years. Interviews were transcribed, confirmed, and analyzed after being recorded. The average age of the sample was 22.15 ± 3.48 years and one-fourth of the participants' disability was due to cerebral palsy and 35% participants used wheelchairs. All the factors promoted inclusive education and equal opportunities for both disabled and nondisabled students. This study reveals that in order to improve the learning experiences of students with disabilities (SwD) and to give them more opportunities for success, it is important to consider all the barriers discussed in this study. It can be concluded that high effort is required to transform the higher educational institutions to be more accommodating for students with disabilities.

Factors Associated with Lifestyle Behaviors among University Students-A Cross-Sectional Study.

Lifestyle behaviors are daily habits influenced by social and environmental factors. This study examined lifestyle behaviors and their associations with sociodemographics, comorbidities, and pain in Saudi university students during the academic year 2021 and 2022. All students received the study invitation via university emails to complete an online questionnaire. The questionnaire included four sections (sociodemographics, health-related information, desired health promotion activities, and a lifestyle behavior assessment) via Health-Promoting Lifestyle Profile II (HPLP-II). The associations between study variables were assessed using Pearson's correlation and multiple linear regression. The study questionnaire was completed by 1112 students. No correlation was found between sociodemographics and lifestyle-behavior-related factors except for students in the College of Science who appeared to have good lifestyle behaviors (an increase in HPLP II total scores of 3.69). Students with mental health issues have poorer lifestyle behaviors and spend more time sitting (p < 0.00). Students without disabilities have lower scores in health responsibility, physical activity, nutrition, and stress management, while auditory disability specifically lowers health responsibility (p < 0.00). Pain was not associated with any assessed lifestyle behaviors. This study identified several significant correlations and differences between variables such as age, sedentary behavior, sleep duration, disability status, college major, and lifestyle behaviors among PNU students. These findings provide insights into the factors that influence students' health-promoting behaviors and can help guide interventions for promoting healthier lifestyles on campus. Targeted health promotion strategies at an early age could help in decreasing overall noncommunicable disease incidents later in life. The study results should be interpreted taking into consideration that the collected data were cross-sectional and self-reported. In conclusion, the findings of this study clearly demonstrate the need for specific lifestyle and health-promoting programs that are directed toward university students.

Enhanced Apigenin Dissolution and Effectiveness Using Glycyrrhizin Spray-Dried Solid Dispersions Filled in 3D-Printed Tablets.

This study aimed to prepare glycyrrhizin-apigenin spray-dried solid dispersions and develop PVA filament-based 3D printlets to enhance the dissolution and therapeutic effects of apigenin (APN); three formulations (APN1-APN3) were proportioned from 1:1 to 1:3. A physicochemical analysis was conducted, which revealed process yields of 80.5-91% and APN content within 98.0-102.0%. FTIR spectroscopy confirmed the structural preservation of APN, while Powder-XRD analysis and Differential Scanning Calorimetry indicated its transformation from a crystalline to an amorphous form. APN2 exhibited improved flow properties, a lower Angle of Repose, and Carr's Index, enhancing compressibility, with the Hausner Ratio confirming favorable flow properties for pharmaceutical applications. In vitro dissolution studies demonstrated superior performance with APN2, releasing up to 94.65% of the drug and revealing controlled release mechanisms with a lower mean dissolution time of 71.80 min and a higher dissolution efficiency of 19.2% compared to the marketed APN formulation. This signified enhanced dissolution and improved therapeutic onset. APN2 exhibited enhanced antioxidant activity; superior cytotoxicity against colon cancer cells (HCT-116), with a lower IC50 than APN pure; and increased antimicrobial activity. A stability study confirmed the consistency of APN2 after 90 days, as per ICH, with an f2 value of 70.59 for both test and reference formulations, ensuring reliable pharmaceutical development. This research underscores the potential of glycyrrhizin-apigenin solid dispersions for pharmaceutical and therapeutic applications, particularly highlighting the superior physicochemical properties, dissolution behavior, biological activities, and stability of APN2, while the development of a 3D printlet shell offers promise for enhanced drug delivery and therapeutic outcomes in colon cancer treatment, displaying advanced formulation and processing techniques.

Acemannan ameliorates STZ-activated diabetes by attenuating high glucose via inhibiting inflammatory cytokines and apoptosis pathway.

Acemannan, the main polysaccharide in Aloe vera, is a -(1, 4)-acetylated polymannose. According to numerous research findings, acemannan is a viable alternative for the treatment of pathological disorders. Streptozotocin (STZ, 60 mg/kg) administered intraperitoneally caused type 2 diabetes in rats. The current study sought to determine the anti-diabetic efficacy of acemannan (25 and 50 mg/kg) in STZ-injected rats. Different biochemical parameters including HbA1C, glucose and serum insulin, lipid profile, inflammatory markers, antioxidant, oxidative balance, liver function test, glycogen and creatinine, and caspase-3 were evaluated. In addition, a molecular docking study was performed to estimate acemannan's binding affinity to inflammatory markers. Acemannan may be a potent anti-diabetic agent for the treatment of diabetic patients, which will aid in future research into alternative diabetes medications.

Barbigerone prevents scopolamine-induced memory impairment in rats by inhibiting oxidative stress and acetylcholinesterase levels.

The current study was designed for the evaluation of barbigerone on memory loss. In this experimental study, 24 Wistar rats (n = 6) were used. Control rats and scopolamine (SCOP)-treated control group rats were orally administered with 3 ml of 0.5% sodium carboxymethyl cellulose (vehicle), whereas barbigerone was (10 and 20 mg kg-1) administered orally to the rats from the test group. During the 14-day treatment, control group rats were given 3 ml kg-1 day-1 saline, and all other groups were administered SCOP (1 mg kg-1 day-1, i.p.) 1 h after barbigerone p.o. treatment. The spontaneous alternation activities, learning capacities of a rat's memory were tested with Morris water maze and Y-maze. Reduced glutathione, malondialdehyde, acetylcholine esterase (AChE) and catalase (CAT) levels were measured in rat brain tissue as oxidative stress/antioxidant markers. Moreover, the levels of tumour necrosis factor, interleukin-6 (IL-6) and IL-1ß were also estimated. Treatment with barbigerone in SCOP-administered rats dramatically reduced SCOP-induced neurobehavioural deficits, oxidative stress and neuroinflammatory markers, improved endogenous antioxidants, and restored AChE activity. By improving cholinergic function and reducing oxidative damage, barbigerone could mitigate the effects of SCOP-induced changes in the brain.

Neuroprotective Effect of Barbaloin on Streptozotocin-Induced Cognitive Dysfunction in Rats via Inhibiting Cholinergic and Neuroinflammatory Cytokines Pathway-TNF-α/IL-1ß/IL-6/NF-κB.

Streptozotocin (STZ) impairs memory in rats through altering the central nervous systems (CNS) as a result of impaired cholinergic dysfunction, oxidative stress, persistent hyperglycemia, and alterations in the glucagon-like peptide (GLP). In this model cholinergic agonist, antioxidant and antihyperglycemic treatment has been shown to have positive effects. Barbaloin has a variety of pharmacological effects. However, there is no evidence on how barbaloin improves memory dysfunction caused by STZ. Thus, we examined its effectiveness against cognitive damage caused by STZ at a dose of 60 mg/kg i.p. in Wistar rats. Blood glucose levels (BGL) and body weight (BW) were assessed. To assess learning and memory skills, the Y-maze test and Morris water maze (MWM) test were utilized. Superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), and glutathione (GSH) as oxidative stress markers were regulated to reverse the cognitive deterioration, and choline-acetyltransferase (ChAT) and acetyl-cholinesterase (AChE) as indicators of cholinergic dysfunction, nuclear factor kappa-B (NF-κB), IL-1ß (interleukin-1ß), IL-6, and tumor necrosis factor-α (TNF-α) contents were used. Barbaloin treatment thereby significantly decreased the BW and learning and memory capacities, resulting in substantial behavioral improvement in the Y-maze and MWM test. BGL, SOD, CAT, MDA, GSH, AChE, ChAT, NF-κB, IL-6, TNF-α, and IL-1ß levels were also altered. In conclusion, the findings revealed that barbaloin had a protective impact against cognitive dysfunction caused by STZ.

Spinophilin-dependent regulation of GluN2B-containing NMDAR-dependent calcium influx, GluN2B surface expression, and cleaved caspase expression.

N-methyl-d-aspartate receptors (NMDARs) are calcium-permeable ion channels that are ubiquitously expressed within the glutamatergic postsynaptic density. Phosphorylation of NMDAR subunits defines receptor conductance and surface localization, two alterations that can modulate overall channel activity. Modulation of NMDAR phosphorylation by kinases and phosphatases regulates the amount of calcium entering the cell and subsequent activation of calcium-dependent processes. The dendritic spine enriched protein, spinophilin, is the major synaptic protein phosphatase 1 (PP1) targeting protein. Depending on the substrate, spinophilin can act as either a PP1 targeting protein, to permit substrate dephosphorylation, or a PP1 inhibitory protein, to enhance substrate phosphorylation. Spinophilin limits NMDAR function in a PP1-dependent manner. Specifically, we have previously shown that spinophilin sequesters PP1 away from the GluN2B subunit of the NMDAR, which results in increased phosphorylation of Ser-1284 on GluN2B. However, how spinophilin modifies NMDAR function is unclear. Herein, we utilize a Neuro2A cell line to detail that Ser-1284 phosphorylation increases calcium influx via GluN2B-containing NMDARs. Moreover, overexpression of spinophilin decreases GluN2B-containing NMDAR activity by decreasing its surface expression, an effect that is independent of Ser-1284 phosphorylation. In hippocampal neurons isolated from spinophilin knockout animals, there is an increase in cleaved caspase-3 levels, a marker of calcium-associated apoptosis, compared with wildtype mice. Taken together, our data demonstrate that spinophilin regulates GluN2B containing NMDAR phosphorylation, channel function, and trafficking and that loss of spinophilin enhances neuronal cleaved caspase-3 expression.

Butin Mitigates Memory Impairment in Streptozotocin-Induced Diabetic Rats by Inhibiting Oxidative Stress and Inflammatory Responses.

It has been reported from the previous literature that butin restores mitochondrial dysfunction by modulation of oxidative stress and glutamate-induced neurotoxicity in mouse hippocampus HT22 cells. Butin also possesses an anti-Huntington's effect in rats. Considering the current background, this study was designed to evaluate the neuroprotective effect of butin against memory loss caused by streptozotocin (STZ). STZ (40 mg/kg) was intraperitoneally injected into rats. Three days later, diabetic rats were identified and included in the study. A total of 30 rats (12 nondiabetic and 18 diabetics) were grouped as Group A (control-non-diabetic rats) and Group B (STZ diabetic control) were treated with 1 mL of sodium CMC (0.5% w/v). Group C (STZ+ butin 25) were treated with butin 25 mg/kg. Group D (STZ+ butin 50) and Group E (butin per se) were administered with butin 50 mg/kg. Each therapy was administered orally once each day for 15-day. The Morris water maze and the Y-maze behavioural tests were run throughout the experimental programme. Animals were put to death on day 15 and their brains were removed for biochemical assays (CAT, SOD, GSH, MDA, nitrite, acetylcholinesterase (AchE), IL-1, and mitochondrial enzyme complexes). Rats with neurobehavioral impairments brought on by STZ have less spontaneous movement, learning capacity, and memory. Additionally, STZ decreased endogenous antioxidants and increased pro-inflammatory cytokines, nitrite, MDA, and AchE. Neurobehavioral deficits and metabolic markers were dramatically improved by butin.

Factors Affecting Mothers' Adherence to Home Exercise Programs Designed for Their Children with Cerebral Palsy.

Cerebral palsy is a common motor disorder that results in long-term impairment. The purpose of this study was to find out what factors influence Saudi mothers' compliance with their Children with Cerebral Palsy (C-CP) Home Exercise Program (HEP). A self-administered online questionnaire was used to perform this qualitative research study on a group of 113 mothers who had children with CP. The study included mothers with children from birth to 12 years old who had received a HEP prescription from a physiotherapist. The measuring instrument tool was a questionnaire with two sections: demographic characteristics and a questionnaire about the parents' adherence to the HEP. The questionnaire utilized in this study was subjected to a reliability analysis, and the derived Cronbach's alpha was found to be 0.814 for the questionnaire (which had 17 phrases). These results imply that the questionnaire is reliable. A total of 113 responses were received, with 4 incomplete responses being eliminated. The majority of mothers (66.1%) did not follow the HEP, according to the findings of this survey. The demographics of the mothers revealed that 20-25-year-old mothers were more adherent than the other age groups. The findings of this study demonstrated that the physical therapist's treatment of the mother influenced exercise compliance.

Assessment of the Correlation between the Levels of Physical Activity and Technology Usage among Children with Down Syndrome in the Riyadh Region.

Background: Children with Down Syndrome (C-DS) have language, cognitive and communication difficulties, in addition to consistent physical inactivity that contributes to poor health and higher-disability-adjusted life years. The purpose of this study was to determine the correlation between the use of electronic technology and levels of physical activity in C-DS in the Riyadh region of Saudi Arabia. Methods: A cross-sectional study was conducted with 49 mothers, where each had a child (6-12 years of age) with Down Syndrome (DS), and who were recruited using purposive sampling from three DS centers in Riyadh, Saudi Arabia. The Children's Physical Activity Questionnaire and Research Questionnaire on the Impact of Technology on Children were used. Descriptive statistics were used to describe the demographics. Pearson's correlation, Student's t-test and the Chi-square test were used to assess the association between technology use, physical activity levels and socio-demographic variables. Results: There was no significant correlation between physical activity and the use of technology by C-DS. However, there was a negative correlation between a high level of physical activity and technology use (R = -0.037). Although, no significant correlation between the mother's characteristics and technology use was found; there was a significantly positive correlation (p = 0.05) between the education level of mothers and the technology use by C-DS. Nonetheless, there was no association between the physical activity level and the gender of the child with DS. Conclusions: This study found that no significant relationship exists between the use of electronic gadgets and the level of physical activity in C-DS.

Head-to-head comparison of the immunogenicity of RotaTeq and Rotarix rotavirus vaccines and factors associated with seroresponse in infants in Bangladesh: a randomised, controlled, open-label, parallel, phase 4 trial.

BACKGROUND: A head-to-head comparison of the most widely used oral rotavirus vaccines has not previously been done, particularly in a high child mortality setting. We therefore aimed to compare the immunogenicity of RotaTeq (Merck, Kenilworth, NJ, USA) and Rotarix (GlaxoSmithKline, Rixensart, Belgium) rotavirus vaccines in the same population and examined risk factors for low seroresponse. METHODS: We did a randomised, controlled, open-label, parallel, phase 4 trial in urban slums within Mirpur and Mohakahli (Dhaka, Bangladesh). We enrolled eligible participants who were healthy infants aged 6 weeks and full-term (ie, >37 weeks' gestation). We randomly assigned participants (1:1), using block randomisation via a computer-generated electronic allocation with block sizes of 8, 16, 24, and 32, to receive either three RotaTeq vaccine doses at ages 6, 10, and 14 weeks or two Rotarix doses at ages 6 and 10 weeks without oral poliovirus vaccine. Coprimary outcomes were the rotavirus-specific IgA seroconversion in both vaccines, and the comparison of the rotavirus IgA seroconversion by salivary secretor phenotype in each vaccine arm. Seroconversion at age 18 weeks in the RotaTeq arm and age of 14 weeks in the Rotarix arm was used to compare the complete series of each vaccine. Seroconversion at age 14 weeks was used to compare two RotaTeq doses versus two Rotarix doses. Seroconversion at age 22 weeks was used to compare the immunogenicity at the same age after receiving the full vaccine series. Safety was assessed for the duration of study participation. This study is registered with ClinicalTrials.gov, NCT02847026. FINDINGS: Between Sept 1 and Dec 8, 2016, a total of 1144 infants were randomly assigned to either the RotaTeq arm (n=571) or Rotarix arm (n=573); 1080 infants (531 in the RotaTeq arm and 549 in the Rotarix arm) completed the study. Rotavirus IgA seroconversion 4 weeks after the full series occurred in 390 (73%) of 531 infants age 18 weeks in the RotaTeq arm and 354 (64%) of 549 infants age 14 weeks in the Rotarix arm (p=0·01). At age 14 weeks, 4 weeks after two doses, RotaTeq recipients had lower seroconversion than Rotarix recipients (268 [50%] of 531 vs 354 [64%] of 549; p<0·0001). However, at age 22 weeks, RotaTeq recipients had higher seroconversion than Rotarix recipients (394 [74%] of 531 vs 278 [51%] of 549; p<0·0001). Among RotaTeq recipients, seroconversion 4 weeks after the third dose was higher than after the second dose (390 [73%] of 531 vs 268 [50%] of 531; p<0·0001]. In the RotaTeq arm, rotavirus IgA seroconversion was lower in non-secretors than in secretors at ages 14 weeks (p=0·08), 18 weeks (p=0·01), and 22 weeks (p=0·02). Similarly, in the Rotarix arm, rotavirus IgA seroconversion was lower in non-secretors than in secretors at ages 14 weeks (p=0·02) and 22 weeks (p=0·01). 65 (11%) of 571 infants had adverse events in the RotaTeq arm compared with 63 (11%) of 573 infants in the Rotarix arm; no adverse events were attributed to the use of either vaccine. One death due to aspiration occurred in the RotaTeq arm, which was not related to the vaccine. INTERPRETATION: RotaTeq induced a higher magnitude and longer duration of rotavirus IgA response than Rotarix in this high child mortality setting. Additional vaccination strategies should be evaluated to overcome the suboptimal performance of current oral rotavirus vaccines in these settings. FUNDING: US Centers for Disease Control and Prevention.

One Full or Two Fractional Doses of Inactivated Poliovirus Vaccine for Catch-up Vaccination in Older Infants: A Randomized Clinical Trial in Bangladesh.

BACKGROUND: The polio eradication endgame called for the removal of trivalent oral poliovirus vaccine (OPV) and introduction of bivalent (types 1 and 3) OPV and inactivated poliovirus vaccine (IPV). However, supply shortages have delayed IPV administration to tens of millions of infants, and immunogenicity data are currently lacking to guide catch-up vaccination policies. METHODS: We conducted an open-label randomized clinical trial assessing 2 interventions, full or fractional-dose IPV (fIPV, one-fifth of IPV), administered at age 9-13 months with a second dose given 2 months later. Serum was collected at days 0, 60, 67, and 90 to assess seroconversion, priming, and antibody titer. None received IPV or poliovirus type 2-containing vaccines before enrolment. RESULTS: A single fIPV dose at age 9-13 months yielded 75% (95% confidence interval [CI], 6%-82%) seroconversion against type 2, whereas 2 fIPV doses resulted in 100% seroconversion compared with 94% (95% CI, 89%-97%) after a single full dose (P < .001). Two doses of IPV resulted in 100% seroconversion. CONCLUSIONS: Our study confirmed increased IPV immunogenicity when administered at an older age, likely due to reduced interference from maternally derived antibodies. Either 1 full dose of IPV or 2 doses of fIPV could be used to vaccinate missed cohorts, 2 fIPV doses being antigen sparing and more immunogenic. CLINICAL TRIAL REGISTRATION: NCT03890497.

A rare case of grave's disease after SARS-CoV-2 vaccine: is it an adjuvant effect?

The COVID-19 virus has been responsible for the development of several systemic diseases. Recently, the COVID-19 vaccine has also been incriminated in the development of autoimmune diseases. Currently, researchers have focused on the relationship between the COVID-19 vaccine and the activation of autoimmune phenomenon. We report a case of Graves' disease (GD) whose symptoms appeared 3 days after vaccination against COVID-19. A forty-three-year-old female, without pathological history, presented with diarrhea and palpitation. She received her first SARS-CoV-2 Vaccine dose (Pfizer-BioNTech), in August 2021. Three days after the vaccine, she felt palpitations, sleep disorders, muscle weakness, and heat intolerance. On examination, her pulse was 119 beats per minute, she weighed 63 kg, and she had lost 4 kg in only two months. GD was suspected. Thyroid hormone testing showed low thyroid-stimulating hormone, and an elevated serum free thyroxine hormone T4 level. Serology tests were positive for TSH receptor autoantibodies (TRAB). A GD induced by adjuvants of SARS-CoV-2 vaccine has been retained as a final diagnosis. Several autoimmune diseases have been attributed to adjuvant-induced autoimmune/inflammatory syndrome, including systemic sclerosis, systemic lupus erythematosus and rheumatoid arthritis, and recently few cases of GD have been explained by this phenomenon.

Antibody persistence and immune memory response following primary vaccination and boosting with live attenuated SA 14-14-2 Japanese encephalitis vaccine (CD-JEV) in Bangladesh: A phase 4 open-label clinical trial.

INTRODUCTION: Japanese encephalitis (JE) virus is one of the leading causes of viral encephalitis across temperate and tropical zones of Asia. The live attenuated SA 14-14-2 JE vaccine (CD-JEV) is one of three vaccines prequalified by the World Health Organization (WHO) to prevent JE. WHO currently recommends a single CD-JEV dose for infants in endemic settings. However, in the absence of long-term immunogenicity data, WHO has indicated a need for long-term immunogenicity studies to inform optimal dosing schedules and determine the need for booster doses. METHODS: This Phase 4, open-label clinical study measured neutralizing antibody (NAb) titers in Bangladeshi children three and four years after primary CD-JEV vaccination and 7 and 28 days after a booster CD-JEV vaccination given four years after primary vaccination. The study also assessed the tolerability and safety of the booster dose. A NAb titer of ≥1:10 was considered seroprotective. RESULTS: Of 560 children vaccinated between 10 and 12 months of age with CD-JEV three years earlier and enrolled in this study from 30 July 2015 through 03 January 2016, 52 (9.3%; 95% CI: 7.2-12.0) had a seroprotective titer at enrollment. One year later, of 533 children, 66 (12.4%; 95% CI: 9.9-15.5) had a seroprotective titer before receiving a booster dose. Of 524 children who received a booster CD-JEV dose, 479 (91.4%; 95% CI: 88.7-93.5) and 514 (98.1%; 95% CI: 96.5-99.0) were seroprotected 7 and 28 days later, respectively. The geometric mean titer (GMT) was 6 (95% CI: 6-6) at baseline, 105 (95% CI: 93-119) 7 days post-booster, and 167 (95% CI: 152-183) 28 days post-booster. No vaccine-associated neurologic adverse events or other serious adverse events were noted following the booster dose. CONCLUSIONS: Although most children did not have measurable antibody titers three and four years after a single primary CD-JEV dose, more than 90% of seronegative children had a strong anamnestic response within one week of a booster dose. This suggests that these children were immune despite the absence of measurable NAb prior to their booster.ClinicalTrials.gov Identifier: NCT02514746.

Multiscale model for forecasting Sabin 2 vaccine virus household and community transmission.

Since the global withdrawal of Sabin 2 oral poliovirus vaccine (OPV) from routine immunization, the Global Polio Eradication Initiative (GPEI) has reported multiple circulating vaccine-derived poliovirus type 2 (cVDPV2) outbreaks. Here, we generated an agent-based, mechanistic model designed to assess OPV-related vaccine virus transmission risk in populations with heterogeneous immunity, demography, and social mixing patterns. To showcase the utility of our model, we present a simulation of mOPV2-related Sabin 2 transmission in rural Matlab, Bangladesh based on stool samples collected from infants and their household contacts during an mOPV2 clinical trial. Sabin 2 transmission following the mOPV2 clinical trial was replicated by specifying multiple, heterogeneous contact rates based on household and community membership. Once calibrated, the model generated Matlab-specific insights regarding poliovirus transmission following an accidental point importation or mass vaccination event. We also show that assuming homogeneous contact rates (mass action), as is common of poliovirus forecast models, does not accurately represent the clinical trial and risks overestimating forecasted poliovirus outbreak probability. Our study identifies household and community structure as an important source of transmission heterogeneity when assessing OPV-related transmission risk and provides a calibratable framework for expanding these analyses to other populations. Trial Registration: ClinicalTrials.gov This trial is registered with clinicaltrials.gov, NCT02477046.

Predictive factors associated with complete pathological response after neoadjuvant treatment for rectal cancer.

PURPOSE: A proportion of 10 to 30% of patients treated by chemoradiotherapy followed by total mesorectal excision surgery for a locally advanced rectal cancer can achieve a complete pathological response. We aimed to identify predictive factors associated with complete pathological response or no response and to assess the impact of each response on survival rates. PATIENTS AND METHODS: Patients treated with long course chemoradiotherapy for locally advanced and/or node positive rectal cancer from 2010 to 2016 were retrospectively reviewed. Statistical analysis was carried out to determine predictors of tumor regression and treatment outcomes. RESULTS: Records were available on 70 patients. In the univariate analysis, clinical factors associated with complete tumor response were tumor mobility in digital rectal examination (P=0.047), a limited parietal invasion (P=0.001), clinically negative lymph node (P<0.001) and a circumferential extent greater than 50% (P=0.001). On the other hand, a T4 classification and an endoscopic tumor size greater than 6cm were associated with no response to treatment (P=0.049 and P=0.017 respectively). On multivariate analysis, T2 clinical classification and N0 statement before treatment were independent predictive factors of pathologic complete response (P<0.001 and P=0.001) and a delayed surgery after 12 weeks was associated with no response to treatment (P=0.001). CONCLUSION: The identification of predictive factors of histological response may help clinicians to predict the prognosis and to propose organ preservation for good responders.

Integrated control of COVID-19 in resource-poor countries.

Low- and middle-income countries (LMICs) face many challenges in controlling COVID-19. Healthcare resources are limited and so are ICU beds. RT-PCR testing is conducted on a limited scale and treatment options are few. There is no vaccine. Therefore, what low-cost solutions remain for the prevention, diagnosis, and treatment of SARS-CoV-2? How should these essential health services be delivered in order to reach the most vulnerable in our societies? In this editorial we discuss several important strategies for controlling COVID-19 including: vaccination, molecular and serological diagnostics, hygiene and WaSH interventions, and low-cost therapeutics. We also discuss the delivery of such services in order to reach the most in need. The proposed integrated control strategy requires immediate action and political will in order to reduce the widening health inequalities caused by the pandemic.

Mechanistic In Situ and Ex Situ Studies of Phase Transformations in Molecular Co-Crystals.

Co-crystallisation is widely explored as a route to improve the physical properties of pharmaceutical active ingredients, but little is known about the fundamental mechanisms of the process. Herein, we apply a hyphenated differential scanning calorimetry-X-ray diffraction technique to mimic the commercial hot melt extrusion process, and explore the heat-induced synthesis of a series of new co-crystals containing isonicotinamide. These comprise a 1:1 co-crystal with 4-hydroxybenzoic acid, 2:1 and 1:2 systems with 4-hydroxyphenylacetic acid and a 1:1 crystal with 3,4-dihydroxyphenylactic acid. The formation of co-crystals during heating is complex mechanistically. In addition to co-crystallisation, conversions between polymorphs of the co-former starting materials and co-crystal products are also observed. A subsequent study exploring the use of inkjet printing and milling to generate co-crystals revealed that the synthetic approach has a major effect on the co-crystal species and polymorphs produced.

Spinophilin regulates phosphorylation and interactions of the GluN2B subunit of the N-methyl-d-aspartate receptor.

N-methyl-d-Aspartate receptors (NMDARs) are abundant postsynaptic proteins that are critical for normal synaptic communication. NMDAR channel function is regulated by multiple properties, including phosphorylation. Inhibition of protein phosphatase 1 (PP1) in hippocampal neurons increases NMDAR activity, an effect abrogated by loss of spinophilin, the major PP1-targeting protein in the postsynaptic density. However, how spinophilin regulates PP1-dependent NMDAR function is unclear. We hypothesize that spinophilin regulates PP1 binding to the NMDAR to alter NMDAR phosphorylation. Our data demonstrate that spinophilin interacts with the GluN2B subunit of the NMDAR. In human embryonic kidney 293 FT cells, activation and/or overexpression of protein kinase A increased the association between spinophilin and the GluN2B subunit of the NMDAR. Functionally, we found that spinophilin overexpression decreased PP1 binding to the GluN2B subunit of the NMDAR and attenuated the PP1-dependent dephosphorylation of GluN2B at Ser-1284. Moreover, in P28 hippocampal lysates isolated from spinophilin KO compared to WT mice, there was increased binding of GluN2B to PP1, decreased phosphorylation of GluN2B at Ser-1284, and altered GluN2B protein interactions with postsynaptic density-enriched proteins. Together, our data demonstrate that spinophilin decreases PP1 binding to GluN2B and concomitantly enhances the phosphorylation of GluN2B at Ser-1284. The putative consequences of these spinophilin-dependent alterations in GluN2B phosphorylation and interactions on synaptic GluN2B localization and function are discussed. Open Science: This manuscript was awarded with the Open Materials Badge For more information see: https://cos.io/our-services/open-science-badges/.