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OBJECTIVE/SUBJECTS To determine the autonomic effects of suboccipital release (SOR) during experimentally induced pain, 16 healthy subjects (eight women, eight men) experienced ischemic (forearm postexercise muscle ischemia [PEMI]) and cold (cold pressor test [CPT]) pain. DESIGN Beat-to-beat heart rate (electrocardiogram), mean arterial blood pressure (finger photoplethysmography), baroreflex sensitivity (transfer function analysis), and pain perception were measured. SOR or a sham (modified yaw; 30 cycles/min) was performed in minute 2 of pain. RESULTS PEMI increased blood pressure by 23 ± 2 and 20 ± 2 mmHg; no differences occurred between SOR or yaw. PEMI modestly elevated heart rate during ischemia, followed by significant reduction from baseline with SOR (-3 ± 2 bpm) and yaw (-4 ± 2 bpm); no differences were observed between treatments. CPT increased blood pressure (SOR = 11 ± 1, yaw = 9 ± 2 mmHg) and heart rate (SOR = 10 ± 2, yaw = 8 ± 3 bpm) before SOR and yaw. Neither treatment nor sham blunted blood pressure increases (SOR = 25 ± 2, yaw = 22 ± 2 mmHg) during CPT; both decreased heart rate (SOR = -3 ± 2, yaw = -2 ± 2 bpm) from baseline. PEMI and CPT caused increased pain without treatment modulation. Following pain and manual intervention, SOR increased baroreflex sensitivity in the 0.15-0.35 Hz range and decreased R-R interval power spectral density in the 0.03-0.5 Hz range compared with yaw. To probe potential mechanisms and interactions between manual treatment and a prototypic analgesic, oral aspirin (967 mg) was given 60 minutes before testing to reduce prostaglandin synthesis. Aspirin slightly attenuated pain but neither altered cardiovascular changes to PEMI nor interacted with SOR or yaw. CONCLUSIONS SOR has the capacity to modulate pain-induced autonomic control and regulation. © The Author(s) 2020. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.Importance Coronavirus disease 2019 (COVID-19) is a pandemic with no specific therapeutic agents and substantial mortality. It is critical to find new treatments. Objective To determine whether convalescent plasma transfusion may be beneficial in the treatment of critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Design, Setting, and Participants Case series of 5 critically ill patients with laboratory-confirmed COVID-19 and acute respiratory distress syndrome (ARDS) who met the following criteria severe pneumonia with rapid progression and continuously high viral load despite antiviral treatment; Pao2/Fio2 less then 300; and mechanical ventilation. All 5 were treated with convalescent plasma transfusion. The study was conducted at the infectious disease department, Shenzhen Third People's Hospital in Shenzhen, China, from January 20, 2020, to March 25, 2020; final date of follow-up was March 25, 2020. Clinical outcomes were compared before and after convalese statement about the potential effectiveness of this treatment, and these observations require evaluation in clinical trials.Healthy full-term breastfed infants show a different growth pattern compared to formula fed infants and this can reduce the risk of obesity and metabolic syndrome later in life. The increasing knowledge of breast milk composition led to the hypothesis that high dietary protein intake derived from formula milk feeding could have a role in determining the different growth rates and body composition of formula-fed infants compared to breastfed infants. In efforts to simulate human milk, many studies have investigated the safety of infant formulas with reduced protein levels. Nevertheless, feeding a "very-low" protein infant formula may cause limited protein synthesis during a phase of rapid growth. For this reason, using a low-protein formula with an amino acid composition modified according on the estimated infant requirements was suggested. In this edition of the American Journal of Clinical Nutrition, Kouwenhoven et al. concluded that the use of a modified low protein formula (1.7 g protein/100 kcal) is safe. Therefore, if this data is confirmed by longer follow up, the current European legal standards for protein amount in infant formula could be reduced with a potential reduction of the later risk of childhood obesity. Copyright © The Author(s) 2020.RNA interference (RNAi) is an important phenomenon that has diverse genetic regulatory functions at the pre- and posttranscriptional levels. The major trigger for the RNAi pathway is double-stranded RNA (dsRNA). dsRNA is processed to generate various types of major small noncoding RNAs (ncRNAs) that include microRNAs (miRNAs), small interfering RNAs (siRNAs) and PIWI-interacting RNAs (piRNAs) in Drosophila melanogaster (D. melanogaster). Functionally, these small ncRNAs play critical roles in virtually all biological systems and developmental pathways. Identification and processing of dsRNAs and activation of RNAi machinery are the three major academic interests that surround RNAi research. Mechanistically, some of the important biological functions of RNAi are achieved through (i) supporting genomic stability via degradation of foreign viral genomes; (ii) suppressing the movement of transposable elements and, most importantly, (iii) post-transcriptional regulation of gene expression by miRNAs that contribute to regulation of epigenetic modifications such as heterochromatin formation and genome imprinting. Here, we review various routes of small ncRNA biogenesis, as well as different RNAi-mediated pathways in D. melanogaster with a particular focus on signaling pathways. In addition, a critical discussion of the most relevant and latest findings that concern the significant contribution of small ncRNAs to the regulation of D. melanogaster physiology and pathophysiology is presented. © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email journals.permissions@oup.com.BACKGROUND Gestational diabetes is associated with unfavorable body fat distribution in offspring. However, less is known about the effects across the range of maternal gestational glycemia on offspring abdominal adiposity (AA) in infancy and early childhood. OBJECTIVES This study determined the association between gestational glycemia and offspring AA measured by MRI in the neonatal period and during the preschool years. METHODS Participants were mother-offspring pairs from the GUSTO (Growing Up in Singapore Towards healthy Outcomes) prospective cohort study. Children who underwent MRI within 2 wk postdelivery (n&nbsp;=&nbsp;305) and/or at preschool age, 4.5 y (n&nbsp;=&nbsp;273), and whose mothers had a 2-h 75-g oral-glucose-tolerance test (OGTT) at 26-28 weeks of gestation were included. AA measured by adipose tissue compartment volumes-abdominal superficial (sSAT), deep subcutaneous (dSAT), and internal (IAT) adipose tissue-was quantified from MRI images. RESULTS Adjusting for potential confounders including maternal prepregnancy BMI, each 1-mmol/L increase in maternal fasting glucose was associated with higher SD scores for sSAT (0.66; 95% CI 0.45, 0.86), dSAT (0.65; 95% CI 0.44, 0.87), and IAT (0.64; 95% CI 0.42, 0.86) in neonates. Similarly, each 1-mmol/L increase in 2-h OGTT glucose was associated with higher neonatal sSAT (0.11; 95% CI 0.03, 0.19) and dSAT (0.09; 95% CI 0.00, 0.17). These associations were stronger in female neonates but only persisted in girls between fasting glucose, and sSAT and dSAT at 4.5 y. CONCLUSIONS A positive association between maternal glycemia and neonatal AA was observed across the whole range of maternal mid-gestation glucose concentrations. These findings may lend further support to efforts toward optimizing maternal hyperglycemia during pregnancy. The study also provides suggestive evidence on sex differences in the impact of maternal glycemia, which merits further confirmation in other studies.This trial was registered at clinicaltrials.gov as NCT01174875. Copyright © The Author(s) 2020.Sporadic Creutzfeld-Jakob disease (CJD) is a rare neurodegenerative disorder. It is uniformly fatal. Clinical signs include myoclonus, visual disturbances, cerebellar ataxia, akinetic mutism and pyramidal/extrapyramidal signs in addition to a rapidly progressive dementia. Premortem diagnosis is challenging due to the rarity of the condition and the subsequent low index of suspicion held for it. [https://www.selleckchem.com/products/MK-1775.html Adavosertib] On literature review, isolated language impairment as the first neurological symptom occurs in only about 1% of patients with sporadic CJD (El Tawil et al. (2017, Acta Neurol Scand, 135 316-23)). We present this patient's case, marked for the unusual presentation and the rapidity of decline, to emphasise the need for awareness of CJD as an important differential diagnosis on stroke units. In our case, magnetic resonance imaging findings drove the suspicion of sporadic CJD as the diagnosis. This seems to correlate with other case reports recognising CJD presenting with progressive aphasic disorders (Terrin et al. (2017, Neurol Sci, 38 1535-7); Mandell et al. (1989, Neurology, 39 55-8); Martory et al. (2012, Eur Neurol, 67 360-2)). © The Author(s) 2020. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email journals.permissions@oup.com.Cervical cancer is the fourth most common cancer in women worldwide, and prognosis is poor for those who experience recurrence or develop metastatic disease, in part due to the lack of active therapeutic directions. The National Cancer Institute convened a Cervical Cancer Clinical Trials Planning Meeting (CTPM) in October 2018 to facilitate the design of hypothesis-driven clinical trials focusing on locally advanced, metastatic and recurrent cervical cancer around the theme of enhancing susceptibility to DNA repair inhibition and DNA damage. Prior to the meeting, a group of experts in the field summarized available preclinical and clinical data to identify potentially active inducers and inhibitors of DNA. The goals of the CTPM focused on identification of novel experimental strategies capitalizing on DNA damage and repair (DDR) regulators and cell cycle aberrations, optimization of radiotherapy as a DDR agent, and design of clinical trials incorporating DDR regulation into the primary and recurrent/metastatic therapies for cervical carcinoma. Meeting deliverables were novel clinical trial concepts to move into the National Clinical Trials Network. This report provides an overview for the rationale of this meeting and the state of the science related to DDR regulation in cervical cancer. © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email journals.permissions@oup.com.BACKGROUND Several risk factors in the first 1000 d are linked with increased obesity risk in later childhood. The role of potentially modifiable eating behaviors in this association is unclear. OBJECTIVES This study examined whether the association between cumulated risk factors in the first 1000 d and adiposity at 6 y is moderated by eating behaviors. METHODS Participants were 302 children from the GUSTO (Growing Up in Singapore Towards healthy Outcomes) cohort. Risk factors included maternal prepregnancy and paternal overweight, excessive gestational weight gain, raised fasting plasma glucose during pregnancy, short breastfeeding duration, and early introduction of solid foods. Composite risk scores reflecting the prevalence and the importance of the risk factors present were computed. Adiposity outcomes were child BMI and sum of skinfolds (SSF), and candidate eating behavior moderators were portion size, eating rate, and energy intake during lunch and in an eating in the absence of hunger task. RESULTS Higher composite risk score predicted higher BMI z scores (B&nbsp;=&nbsp;0.