Neurodevelopmental changes of fetal pain

Pain in the developing fetus is controversial because of the difficulty in measuring and interpreting pain during gestation. It has received increased attention lately because of recently introduced legislation that would require consideration of fetal pain during intentional termination of pregnancy. During development, sensory fibers are abundant by 20 weeks; a functional spinal reflex is present by 19 weeks; connections to the thalamus are present by 20 weeks; and connections to subplate neurons are present by 17 weeks with intensive differentiation by 25 weeks. These cells are important developmentally, but decline as a result of natural apoptosis. Mature thalamocortical projections are not present until 29 to 30 weeks, which has led many to believe the fetus does not experience emotional "pain" until then. Pain requires both nociception and emotional reaction or interpretation. Nociception causes physiologic stress, which in turn causes increases in catecholamines, cortisol, and other stress hormones. Physiological stress is different from the emotional pain felt by the more mature fetus or infant, and this stress is mitigated by pain medication such as opiates. The plasticity of the developing brain makes it vulnerable to the stressors that cause long-term developmental changes, ultimately leading to adverse neurological outcomes. Whereas evidence for conscious pain perception is indirect, evidence for the subconscious incorporation of pain into neurological development and plasticity is incontrovertible. Scientific data, not religious or political conviction, should guide the desperately needed research in this field. In the meantime, it seems prudent to avoid pain during gestation.     

Current controversies regarding pain assessment in neonates

Although over 40 methods of pain assessment in infants are available for use in clinical practice, unrecognized and under-treated pain remains one of the most commonly reported problems within the Neonatal Intensive Care Units. A number of factors have been found to account for differences in the robustness of the pain response in neonates of varying gestational ages. Discrepancies between behavioral and physiological pain indicators have also been reported. With newer technologies, there is an opportunity not only to verify infant pain perception, but these tools may allow an identification of which of the observed indicators are most sensitive in particular clinical situations. The current controversies regarding pain assessment in preterm and term infants are reviewed to define the most important issues and to develop a dialogue for future directions.     

Premedication for tracheal intubation in neonates: confusion or controversy?

Tracheal intubation is performed frequently in the NICU and delivery room. This procedure is extremely distressing, painful, and has the potential for airway injury. Premedication with sedatives, analgesics, and muscle relaxants is standard practice for pediatric and adult intubation, yet the use of these drugs is not common for intubation in neonates. The risks and benefits of using premedications for intubating unstable newborns are hotly debated, although recent evidence shows that premedication for non-urgent or semi-urgent intubations is safer and more effective than awake intubations. This article reviews clinical practices reported in surveys on premedication for neonatal intubation, the physiological effects of laryngoscopy and intubation on awake neonates, as well as the clinical and physiological effects of different drug combinations used for intubation. A wide variety of drugs, either alone or in combination, have been used as premedication for elective intubation in neonates. Schematically, these studies have been of three main types: (a) studies comparing awake intubation versus those with sedation or analgesia, (b) studies comparing different premedication regimens comprising sedatives, analgesics, and anesthetics, and (c) case series of neonates in which some authors have reported their experience with a specific premedication regimen. The clinical benefits described in these studies and the need for pain control in neonates make the case for using appropriate premedication routinely for elective or semi-urgent intubations. Tracheal intubation without the use of analgesia or sedation should be performed only for urgent resuscitations in the delivery room or other life-threatening situations when intravenous access is unavailable.     

Resistance Exercise Training Improves Metabolic and Inflammatory Control in Adipose and Muscle Tissues in Mice Fed a High-Fat Diet

This study investigates whether ladder climbing (LC), as a model of resistance exercise, can reverse whole-body and skeletal muscle deleterious metabolic and inflammatory effects of high-fat (HF) diet-induced obesity in mice. To accomplish this, Swiss mice were fed for 17 weeks either standard chow (SC) or an HF diet and then randomly assigned to remain sedentary or to undergo 8 weeks of LC training with progressive increases in resistance weight. Prior to beginning the exercise intervention, HF-fed animals displayed a 47% increase in body weight (BW) and impaired ability to clear blood glucose during an insulin tolerance test (ITT) when compared to SC animals. However, 8 weeks of LC significantly reduced BW, adipocyte size, as well as glycemia under fasting and during the ITT in HF-fed rats. LC also increased the phosphorylation of Akt_Ser473 and AMPK_Thr172 and reduced tumor necrosis factor-alpha (TNF-α) and interleukin 1 beta (IL1-β) contents in the quadriceps muscles of HF-fed mice. Additionally, LC reduced the gene expression of inflammatory markers and attenuated HF-diet-induced NADPH oxidase subunit gp91phox in skeletal muscles. LC training was effective in reducing adiposity and the content of inflammatory mediators in skeletal muscle and improved whole-body glycemic control in mice fed an HF diet.     

Contrast-enhanced flair imaging in the evaluation of infectious leptomeningeal diseases

PURPOSE: The purpose of our study was to compare contrast-enhanced fluid-attenuated inversion recovery (FLAIR) images with contrast-enhanced T1 weighted images for infectious leptomeningitis. MATERIALS AND METHODS: We studied twenty-four patients with a clinical suspicion of infectious meningitis with unenhanced FLAIR, contrast-enhanced T1 weighted and contrast-enhanced FLAIR MR sequences. Twelve patients had cytologic and biochemical diagnosis of meningitis on cerebrospinal fluid (CSF) examination obtained 48 h before or after the MR study. Sequences were considered positive if abnormal signal was seen in the subarachnoid space (cistern or sulci) or along pial surface. RESULTS: Twenty-seven examinations in 24 patients were performed. Of the 12 patients (thirteen studies) in whom cytology was positive, unenhanced FLAIR images were positive in six cases (sensitivity 46%), contrast-enhanced FLAIR images were positive in 11 (sensitivity 85%), and contrast-enhanced T1 weighted MR images were positive in 11 patients (sensitivity 85%). Of the 12 patients (14 studies) in whom cerebrospinal fluid study was negative, unenhanced FLAIR images were negative in 13, contrast-enhanced FLAIR images were negative in 11, and contrast-enhanced T1 weighted MR images were negative in eight. Thus, the specificity of unenhanced FLAIR, contrast-enhanced FLAIR and contrast-enhanced T1 weighted images was 93, 79 and 57%, respectively. CONCLUSION: Our results suggest that post-contrast FLAIR images have similar sensitivity but a higher specificity compared to contrast-enhanced T1 weighted images for detection of leptomeningeal enhancement. It can be a useful adjunct to post-contrast T1 weighted images in evaluation of infectious leptomeningitis.     

A Current Review of Cypermethrin-Induced Neurotoxicity and Nigrostriatal Dopaminergic Neurodegeneration

Cypermethrin, a class II pyrethroid pesticide, is used to control insects in the household and agricultural fields. Despite beneficial roles, its uncontrolled and repetitive applications lead to unintended effects in non-target organisms. Cypermethrin crosses the blood-brain barrier and induces neurotoxicity and motor deficits. Cypermethrin prolongs the opening of sodium channel, a major site of its action, leading to hyper-excitation of the central nervous system. In addition to sodium channel, cypermethrin modulates chloride, voltage-gated calcium and potassium channels, alters the activity of glutamate and acetylcholine receptors and adenosine triphosphatases and induces DNA damage and oxidative stress in the neuronal cells. Cypermethrin also modulates the level of neurotransmitters, including gamma-aminobutyric acid and dopamine. It is one of the most commonly used pesticides in neurotoxicology research not only because of its variable responses depending upon the doses, time and routes of exposure and strain, age, gender and species of animals used across multiple studies but also owing to its ability to induce the nigrostriatal dopaminergic neurodegeneration. This article describes the effect of acute, chronic, developmental and adulthood exposures to cypermethrin in experimental animals. The article sheds light on cypermethrin-induced changes in the central nervous system, including its contribution in the onset of specific features, which are associated with the nigrostriatal dopaminergic neurodegeneration. Resemblances and dissimilarities of cypermethrin-induced nigrostriatal dopaminergic neurodegeneration with sporadic and chemicals-induced disease models along with its advantages and pitfalls are also discussed.     

Evidence-Based Strategies for the Treatment of Peritoneal Malignancies during Health Care Resource Restriction: The COVID-19 Pandemic

Background: The COVID-19 pandemic has put enormous pressure on hospital resources, and has affected all aspects of patient care. As operative volumes decrease, cancer surgeries must be triaged and prioritized with careful thought and attention to ensure maximal benefit for the maximum number of patients. Peritoneal malignancies present a unique challenge, as surgical management can be resource intensive, but patients have limited non-surgical treatment options. This review summarizes current data on outcomes and resource utilization to help inform decision-making and case prioritization in times of constrained health care resources. Methods: A rapid literature review was performed, examining surgical and non-surgical outcomes data for peritoneal malignancies. Narrative data synthesis was cross-referenced with relevant societal guidelines. Peritoneal malignancy surgeons and medical oncologists reviewed recommendations to establish a national perspective on case triage and mitigating treatment strategies. Results and Conclusions: Triage of peritoneal malignancies during this time of restricted health care resource is nuanced and requires multidisciplinary discussion with consideration of individual patient factors. Prioritization should be given to patients where delay may compromise resectability of disease, and where alternative treatment options are lacking. Mitigating strategies such as systemic chemotherapy and/or surgical deferral may be utilized with close surveillance for disease stability or progression, which may affect surgical urgency. Unique hospital capacity, and ability to manage the complex post-operative course for these patients must also be considered to ensure patient and system needs are aligned.