Allometric rules for mammalian cortical layer 5 neuron biophysics.

The biophysical properties of neurons are the foundation for computation in the brain. Neuronal size is a key determinant of single neuron input-output features and varies substantially across species1-3. However, it is unknown whether different species adapt neuronal properties to conserve how single neurons process information4-7. Here we characterize layer 5 cortical pyramidal neurons across 10 mammalian species to identify the allometric relationships that govern how neuronal biophysics change with cell size. In 9 of the 10 species, we observe conserved rules that control the conductance of voltage-gated potassium and HCN channels. Species with larger neurons, and therefore a decreased surface-to-volume ratio, exhibit higher membrane ionic conductances. This relationship produces a conserved conductance per unit brain volume. These size-dependent rules result in large but predictable changes in somatic and dendritic integrative properties. Human neurons do not follow these allometric relationships, exhibiting much lower voltage-gated potassium and HCN conductances. Together, our results in layer 5 neurons identify conserved evolutionary principles for neuronal biophysics in mammals as well as notable features of the human cortex.

Atypical behaviour and connectivity in SHANK3-mutant macaques.

Mutation or disruption of the SH3 and ankyrin repeat domains 3 (SHANK3) gene represents a highly penetrant, monogenic risk factor for autism spectrum disorder, and is a cause of Phelan-McDermid syndrome. Recent advances in gene editing have enabled the creation of genetically engineered non-human-primate models, which might better approximate the behavioural and neural phenotypes of autism spectrum disorder than do rodent models, and may lead to more effective treatments. Here we report CRISPR-Cas9-mediated generation of germline-transmissible mutations of SHANK3 in cynomolgus macaques (Macaca fascicularis) and their F1 offspring. Genotyping of somatic cells as well as brain biopsies confirmed mutations in the SHANK3 gene and reduced levels of SHANK3 protein in these macaques. Analysis of data from functional magnetic resonance imaging revealed altered local and global connectivity patterns that were indicative of circuit abnormalities. The founder mutants exhibited sleep disturbances, motor deficits and increased repetitive behaviours, as well as social and learning impairments. Together, these results parallel some aspects of the dysfunctions in the SHANK3 gene and circuits, as well as the behavioural phenotypes, that characterize autism spectrum disorder and Phelan-McDermid syndrome.

COVID-19 Creating another problem? Sustainable solution for PPE disposal through LCA approach.

Amid COVID-19, there have been rampant increase in the use of Personal Protective Equipment (PPE) kits by frontline health and sanitation communities, to reduce the likelihoods of infections. The used PPE kits, potentially being infectious, pose a threat to human health, terrestrial, and marine ecosystems, if not scientifically handled and disposed. However, with stressed resources on treatment facilities and lack of training to the health and sanitation workers, it becomes vital to vet different options for PPE kits disposal, to promote environmentally sound management of waste. Given the various technology options available for treatment and disposal of COVID-19 patients waste, Life Cycle Assessment, i.e., cradle to grave analysis of PPE provides essential guidance in identifying the environmentally sound alternatives. In the present work, Life Cycle Assessment of PPE kits has been performed using GaBi version 8.7 under two disposal scenarios, namely landfill and incineration (both centralized and decentralized) for six environmental impact categories covering overall impacts on both terrestrial and marine ecosystems, which includes Global Warming Potential (GWP), Human Toxicity Potential (HTP), Eutrophication Potential (EP), Acidification Potential (AP), Freshwater Aquatic Ecotoxicity Potential (FAETP) and Photochemical Ozone Depletion Potential (POCP). Considering the inventories of PPE kits, disposal of PPE bodysuit has the maximum impact, followed by gloves and goggles, in terms of GWP. The use of metal strips in face-mask has shown the most significant HTP impact. The incineration process (centralized-3816 kg CO2 eq. and decentralized-3813 kg CO2 eq.) showed high GWP but significantly reduced impact w.r.t. AP, EP, FAETP, POCP and HTP, when compared to disposal in a landfill, resulting in the high overall impact of landfill disposal compared to incineration. The decentralized incineration has emerged as environmentally sound management option compared to centralized incinerator among all the impact categories, also the environmental impact by transportation is significant (2.76 kg CO2 eq.) and cannot be neglected for long-distance transportation. Present findings can help the regulatory authority to delineate action steps for safe disposal of PPE kits.

Effect of distracting faces on visual selective attention in the monkey.

In primates, visual stimuli with social and emotional content tend to attract attention. Attention might be captured through rapid, automatic, subcortical processing or guided by slower, more voluntary cortical processing. Here we examined whether irrelevant faces with varied emotional expressions interfere with a covert attention task in macaque monkeys. In the task, the monkeys monitored a target grating in the periphery for a subtle color change while ignoring distracters that included faces appearing elsewhere on the screen. The onset time of distracter faces before the target change, as well as their spatial proximity to the target, was varied from trial to trial. The presence of faces, especially faces with emotional expressions interfered with the task, indicating a competition for attentional resources between the task and the face stimuli. However, this interference was significant only when faces were presented for greater than 200 ms. Emotional faces also affected saccade velocity and reduced pupillary reflex. Our results indicate that the attraction of attention by emotional faces in the monkey takes a considerable amount of processing time, possibly involving cortical-subcortical interactions. Intranasal application of the hormone oxytocin ameliorated the interfering effects of faces. Together these results provide evidence for slow modulation of attention by emotional distracters, which likely involves oxytocinergic brain circuits.

ß2-Adrenergic receptor agonist ameliorates phenotypes and corrects microRNA-mediated IGF1 deficits in a mouse model of Rett syndrome.

Rett syndrome is a severe childhood onset neurodevelopmental disorder caused by mutations in methyl-CpG-binding protein 2 (MECP2), with known disturbances in catecholamine synthesis. Here, we show that treatment with the ß2-adrenergic receptor agonist clenbuterol increases survival, rescues abnormalities in respiratory function and social recognition, and improves motor coordination in young male Mecp2-null (Mecp2(-/y)) mice. Importantly, we demonstrate that short-term treatment with clenbuterol in older symptomatic female heterozygous (Mecp2(-/+)) mice rescues respiratory, cognitive, and motor coordination deficits, and induces an anxiolytic effect. In addition, we reveal abnormalities in a microRNA-mediated pathway, downstream of brain-derived neurotrophic factor that affects insulin-like growth factor 1 (IGF1) expression in Mecp2(-/y) mice, and show that treatment with clenbuterol restores the observed molecular alterations. Finally, cotreatment with clenbuterol and recombinant human IGF1 results in additional increases in survival in male null mice. Collectively, our data support a role for IGF1 and other growth factor deficits as an underlying mechanism of Rett syndrome and introduce ß2-adrenergic receptor agonists as potential therapeutic agents for the treatment of the disorder.

Spatial Attention and Temporal Expectation Under Timed Uncertainty Predictably Modulate Neuronal Responses in Monkey V1.

The brain uses attention and expectation as flexible devices for optimizing behavioral responses associated with expected but unpredictably timed events. The neural bases of attention and expectation are thought to engage higher cognitive loci; however, their influence at the level of primary visual cortex (V1) remains unknown. Here, we asked whether single-neuron responses in monkey V1 were influenced by an attention task of unpredictable duration. Monkeys covertly attended to a spot that remained unchanged for a fixed period and then abruptly disappeared at variable times, prompting a lever release for reward. We show that monkeys responded progressively faster and performed better as the trial duration increased. Neural responses also followed monkey's task engagement-there was an early, but short duration, response facilitation, followed by a late but sustained increase during the time monkeys expected the attention spot to disappear. This late attentional modulation was significantly and negatively correlated with the reaction time and was well explained by a modified hazard function. Such bimodal, time-dependent changes were, however, absent in a task that did not require explicit attentional engagement. Thus, V1 neurons carry reliable signals of attention and temporal expectation that correlate with predictable influences on monkeys' behavioral responses.

Analysis of heterogeneous gallstones using laser-induced breakdown spectroscopy (LIBS) and wavelength dispersive X-ray fluorescence (WD-XRF).

Laser-induced breakdown spectroscopy (LIBS) is an emerging analytical technique with numerous advantages such as rapidity, multi-elemental analysis, no specific sample preparation requirements, non-destructiveness, and versatility. It has been proven to be a robust elemental analysis tool attracting interest because of being applied to a wide range of materials including biomaterials. In this paper, we have performed spectroscopic studies on gallstones which are heterogeneous in nature using LIBS and wavelength dispersive X-ray fluorescence (WD-XRF) techniques. It has been observed that the presence and relative concentrations of trace elements in different kind of gallstones (cholesterol and pigment gallstones) can easily be determined using LIBS technique. From the experiments carried out on gallstones for trace elemental mapping and detection, it was found that LIBS is a robust tool for such biomedical applications. The stone samples studied in the present paper were classified using the Fourier transform infrared (FTIR) spectroscopy. WD-XRF spectroscopy has been applied for the qualitative and quantitative analysis of major and trace elements present in the gallstone which was compared with the LIBS data. The results obtained in the present paper show interesting prospects for LIBS and WD-XRF to study cholelithiasis better.

Imaging prior information in the brain.

In making sense of the visual world, the brain's processing is driven by two factors: the physical information provided by the eyes ("bottom-up" data) and the expectancies driven by past experience ("top-down" influences). We use degraded stimuli to tease apart the effects of bottom-up and top-down processes because they are easier to recognize with prior knowledge of undegraded images. Using machine learning algorithms, we quantify the amount of information that brain regions contain about stimuli as the subject learns the coherent images. Our results show that several distinct regions, including high-level visual areas and the retinotopic cortex, contain more information about degraded stimuli with prior knowledge. Critically, these regions are separate from those that exhibit classical priming, indicating that top-down influences are more than feature-based attention. Together, our results show how the neural processing of complex imagery is rapidly influenced by fleeting experiences.

Nucleus basalis-enabled stimulus-specific plasticity in the visual cortex is mediated by astrocytes.

Although cholinergic innervation of the cortex by the nucleus basalis (NB) is known to modulate cortical neuronal responses and instruct cortical plasticity, little is known about the underlying cellular mechanisms. Using cell-attached recordings in vivo, we demonstrate that electrical stimulation of the NB, paired with visual stimulation, can induce significant potentiation of visual responses in excitatory neurons of the primary visual cortex in mice. We further show with in vivo two-photon calcium imaging, ex vivo calcium imaging, and whole-cell recordings that this pairing-induced potentiation is mediated by direct cholinergic activation of primary visual cortex astrocytes via muscarinic AChRs. The potentiation is absent in conditional inositol 1,4,5 trisphosphate receptor type 2 KO mice, which lack astrocyte calcium activation, and is stimulus-specific, because pairing NB stimulation with a specific visual orientation reveals a highly selective potentiation of responses to the paired orientation compared with unpaired orientations. Collectively, these findings reveal a unique and surprising role for astrocytes in NB-induced stimulus-specific plasticity in the cerebral cortex.

Importance of laser-induced breakdown spectroscopy for hard tissues (bone, teeth) and other calcified tissue materials.

Laser-induced breakdown spectroscopy (LIBS) as a sensitive optical technique capable of fast multielemental analysis proved to be a versatile tool in different applications. It became visible in the analytical atomic spectroscopy scene in the late 1980s and since then, its applications having been developed continuously in different field of science and technology including biomedical science. Here, we review the use and importance of LIBS for trace element determination in different calcified tissue materials. In this article, we have also reported a comprehensive review of the recent progress of biomedical applications of LIBS.

Molecular determination of antifolate resistance associated point mutations in Plasmodium falciparum dihydrofolate reductase (dhfr) and dihydropteroate synthetase (dhps) genes among the field samples in Arunachal Pradesh.

BACKGROUND & OBJECTIVES: Antimalarial resistance in P. falciparum malaria parasite creates a serious obstacle in malaria control programme. Keeping this in mind, in the present study antifolate resistance associated point mutations in P. falciparum dihydrofolate reductase (Pfdhfr) and dihydropteroate synthetase (Pfdhps) genes among the field samples in Arunachal Pradesh were determined. METHODS: Blood samples were collected from 145 suspected malaria patients/healthy control subjects in malarious areas of Lohit and Changlang districts of Arunachal Pradesh, India during January 2012 to December 2013. RESULTS: In microscopic slide examination, 51.03% (74/145) were found malaria positive. Plasmodium falciparum mono-infection was observed in 62.16% (46/74) of total malaria positive cases. Polymerase chain reaction (PCR) was employed in all the P. falciparum positive samples for detection of 648 bp of Pfdhfr and 710 bp of Pfdhps genes. All the amplified products were analysed for detection of single nucleotide polymorphisms in dhfr and dhps genes. A total of four different genotypes of Pfdhfr gene were observed, of which double mutant allele ANRNI was mostly prevalent and it was found in 65.22% (30/46) cases. Likewise, four different haplotypes of Pfdhps gene were detected, of which triple mutant allele AGEAA shares 69.57% (32/46) followed by other haplotypes. In Pfdhfr-Pfdhps two locus mutations analysis, two isolates in Changlang district had shown quintuple mutant haplotype AIRNL-AGEAA, likely to be associated with treatment failure. The P. falciparum two locus dhfr-dhps haplotype (ANRNI-AGEAA) was observed in 56.52% (26/46) cases. INTERPRETATION & CONCLUSION: Overall, high grade of sulphadoxine-pyrimethamine resistance associated genetic polymorphisms were observed among the P. falciparum parasite population in Arunachal Pradesh during the study period.

Detection of point mutation in Plasmodium falciparum ATPase6 gene associated with artemisinin resistance from Assam and Arunachal Pradesh.

BACKGROUND & OBJECTIVES: Resistance against partner drugs of artemisinin has been reported from different parts of India. The study aims to find out the single nucleotide polymorphisms in Plasmodium falciparum ATPase6 gene associated with artemisinin resistance. METHODS: Blood samples were collected from 141 patients with P. falciparum monoinfection in malaria endemic zones of Assam and Arunachal Pradesh. A 645 bp portion of PfATPase6 gene was amplified and sequenced to determine the frequency of mutations associated with resistance to artemisinin. RESULTS: Mutations at codon S769N, which have been proposed to confer artemisinin resistance, were not detected in our study samples. Instead of that a novel non-synonymous mutation (C-T) at 1847 bp position resulting in serine to phenylalanine alteration at codon S616F was detected from the P. falciparum field isolates in Changlang district of Arunachal Pradesh, whereas no mutation was detected in any of the analyzed samples in Assam indicating that wild type PfATPase6 genotype was found circulating in this region. Overall, based on the mutational pattern, two haplotypes of PfATPase6 gene were observed during the study, the wild type and mutant S616F allele. The overall haplotype diversity (Hd) was found to be: 0.069 and nucleotide diversity (per site Pi): 0.00012. Highest haplotype diversity was recorded in Changlang district of Arunachal Pradesh having Hd value of 0.33333 along with single polymorphic site and nucleotide diversity (Pi): 0.00060. A pair-wise fixation index (FST) value of 0.16667 indicates great genetic differentiation within the parasite population of Changlang district with the population of Karbi Anglong, Chirang, Tinsukia, Sivasagar, Jorhat, NC Hills, Lakhimpur, Golaghat and Dibrugarh districts of Assam and Lohit district of Arunachal Pradesh. INTERPRETATION & CONCLUSION: A better understanding of the distribution of antimalarial drug resistance with malaria parasite may provide insight into some of the epidemiological determinants of the increasing case burden.

Investigation of polybrominated diphenyl ethers in old consumer products in India.

Polybrominated diphenyl ethers (PBDEs) used extensively over the past 3 decades as flame retardants in most types of polymers, all over the world, have been identified as global pollutants. PBDEs pose various health problems such as thyroid hormone disruption, permanent learning and memory impairment, behavioral changes, hearing deficits, delayed puberty onset, fetal malformations, and possibly cancer. Many measurements of PBDEs in various matrices from Sweden, Holland, Japan, the USA, and elsewhere have been reported, but few measurements are available for India. In this study, a preliminary screening of different congeners of PBDEs has been performed in different old electronic and consumer products with an objective to build capacity in order to analyze PBDEs and BFRs. Six different samples, foam from upholstery, motherboard of a computer, children toy composite sample, old vanishing window blind sample, electrical wire sample, and PVC flooring sample, were collected and analyzed for the presence of the following PBDE congeners: BDE-28, BDE-47, BDE-99, BDE-100, BDE-153, BDE-154, BDE-183, and BDE-209. It was found that three out of six samples were positive for the presence of PBDEs. Three congeners were detected in the samples, i.e., BDE-47, BDE-153, and BDE-209, of which, highest concentration was of BDE-209. Among the samples, motherboard of computer showed the highest concentration of BDE-209 followed by window blind and foam from upholstery. The results of this preliminary investigation indicate that PBDEs are still present in the old consumer products which can be an important additional source of exposure to the population.

Stroke: current concepts.

Cerebrovascular accidents (CVAs) are the leading cause of disability and the fourth leading cause of death in the U.S. The WHO defines stroke as "rapidly developing clinical signs of focal disturbance of cerebral function lasting more than 24 hours with no apparent cause other than of vascular origin." Strokes are subdivided into two major classifications: ischemic (80-87 percent) andhemorrhagic (13-20 percent). Ischemic strokes occur from thrombi, emboli, or global hypoperfusion. Hemorrhagic strokes are either parenchymal (10 percent of all strokes) or subarachnoid (3 percent of all strokes). There are a variety of recognized risk factors for stroke which include: age, race, family history, hypertension, diabetes mellitus, atherosclerosis, cardiac arrhythmias, prosthetic valves, hyperlipidemia, cigarette smoking, and others (drugs or hormones). The initial assessment of a patient suspected of stroke should be done quickly enough to ensure maximal reperfusion of brain tissue. The steps to achieve this goal are: 1) exclude an intracranial hemorrhage, 2) assess for contraindications to thrombolytics, 3) characterize the infarct. The workup for a patient should first include a history (especially the time when neurologic symptoms began), a physical exam (including the NIHSS), and imaging studies (to rule out hemorrhagic components). In addition, several lab studies can also be obtained including: PT/INR, glucose, complete blood count, metabolic panel, creatine kinase, ECG, echocardiogram, lipid panel, carotid Doppler, MRA or CTA. Acute management of a stroke is primarily focused on stabilizing the patient and allowing as much reperfusion as possible for at-risk brain tissue. Stroke management in the acute setting includes: use of thrombolytics if indicated, and re-assessment to monitor progression. Several trials have been completed in pursuit of safety and effectiveness of intra-arterial stroke therapy for patients outside the recommended thrombolytic time window, but so far they are only experimental treatment options. The best preventative measures for first time or recurrent stroke are: starting or switching antiplatelet therapy, treatment of cardiovascular risk factors (atrial fibrillation and carotid stenosis), optimization of hypertension, dyslipidemia and diabetes mellitus management, and smoking cessation.

Degradation of Di- Through Hepta-Chlorobiphenyls in Clophen Oil Using Microorganisms Isolated from Long Term PCBs Contaminated Soil.

Present work describes microbial degradation of selected polychlorinated biphenyls (PCBs) congeners in Clophen oil which is used as transformer oil and contains high concentration of PCBs. Indigenous PCBs degrading bacteria were isolated from Clophen oil contaminated soil using enrichment culture technique. A 15 days study was carried out to assess the biodegradation potential of two bacterial cultures and their consortium for Clophen oil with a final PCBs concentration of 100 mg kg(-1). The degradation capability of the individual bacterium and the consortium towards the varying range of PCBs congeners (di- through hepta-chlorobiphenyls) was determined using GCMS. Also, dehydrogenase enzyme was estimated to assess the microbial activity. Maximum degradation was observed in treatment containing consortium that resulted in up to 97 % degradation of PCB-44 which is a tetra chlorinated biphenyl whereas, hexa chlorinated biphenyl congener (PCB-153) was degraded up to 90 % by the consortium. This indicates that the degradation capability of microbial consortium was significantly higher than that of individual cultures. Furthermore, the results suggest that for degradation of lower as well as higher chlorinated PCB congeners; a microbial consortium is required rather than individual cultures.

Antenatal diagnosis of congenital pouch colon: a case report from the Indian subcontinent with insights into management.

Congenital pouch colon (CPC) is highly uncommon congenital anorectal malformation where a distended pouch-like structure replaces either some part of the colon or the entire colon and communicates to the genitourinary tract through a fistula. Diagnosis of CPC is usually made after birth when neonate/infant presents with abdominal distension and absence of anal opening. Making antenatal diagnosis of CPC is difficult because of the lack of specific and verifiable signs on sonography. Hence, only a few cases of antenatal diagnosis of CPC have been reported.1,2 In our case, CPC was suspected on a routine antenatal growth scan ultrasound in the late third trimester, showing a hypoechoic tubular-shaped lesion in the pre-sacral region. With this suspicion, we suggested an institutional delivery at a tertiary level centre, and diagnosis of type III CPC was confirmed on post-delivery imaging and emergency primary surgery, done on the day 3 of life (pouch resection, division of fistula, and protective colostomy). The child also underwent further corrective surgeries in a staged manner in second year of life and recovered completely. Beforehand diagnosis prevented any unnecessary delay in operative care, reduced postoperative complications, and improved the overall outcome of this otherwise complex condition.

Diffusion-Weighted MRI in Perianal Abscess: Role and Comparison With Contrast-Enhanced MRI.

BACKGROUND: Perianal abscess is a clinical infective and/or inflammatory collection in the perianal region, one entity of a large group of anal and perianal disorders. Perianal abscesses are often seen as a complication of grade 2 and grade 4 perianal fistulas from St. James's University Hospital classification. Several imaging modalities have been tried in the past for adequate assessment of perianal abscess with contrast-enhanced magnetic resonance imaging (CE-MRI) providing the most accurate results. Diffusion-weighted imaging (DWI) is an emerging sequence that can provide comparable results to CE-MRI in diagnosing and characterizing perianal abscess. The main objective of this study is to assess the role of DWI in adequate identification and assessment of perianal abscess and compare the final results with contrast-enhanced images. METHODS: Twenty patients with complicated perianal fistula with clinically suspected perianal abscess were evaluated with DWI and CE-MRI. This study was a comparative cross-sectional study conducted in the Department of Radiodiagnosis and Imaging, All India Institute of Medical Sciences, Bhopal, India. Chi-square test was done to find the association between categorical variables. Kappa test was used to find the agreement between two different tests. Receiver operating characteristics (ROC) analysis was done to estimate the area under the curve in predicting the outcome. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy were used to measure the validity of the tests. RESULTS: DWI is a very sensitive MRI sequence and is equivalent to CE-MRI to detect the location and analyzing the loco-regional extent of abscess in complicated perianal fistula cases. DWI is also very sensitive and superior to T2 short tau inversion recovery (STIR) in differentiating perianal abscess from perianal inflammation without abscess. CONCLUSION: DWI can be used as an alternative to post-contrast fat-suppressed MRI in precisely defining the location and extent of anal and perianal abscesses and disease activity in complicated fistula cases.

Ultrasound Evaluation of Placental Thickness: Insights From an Observational Study and Implications for Fetal Growth Assessment.

Introduction A precise gestational age (GA) assessment is critical to monitoring fetal growth and planning delivery. Any disorder that affects the placenta will affect the fetus. Hence, the placenta serves as an indicator of fetal development. So, placental thickness (PT) measurement can be utilized as a parameter in the precise estimation of gestational age and prediction of the fetal outcome. Ultrasound (USG) remains the preferred method for detecting placental abnormalities due to its benefits. This study aimed to evaluate placental thickness by USG in various GA subgroups and to see the correlation of PT with GA and fetal outcome. Methods Cross-sectional observational study with short follow-up. A total of 296 antenatal women between 14 weeks and 40 weeks underwent USG to measure placental thickness and were followed up until delivery. The collected data was compiled systematically and analyzed using IBM SPSS Statistics for Windows, Version 25 (released 2017; IBM Corp., Armonk, New York, United States). The level of significance was taken as p<0.05. Results The mean placental thickness progressed from 1.8 cm to 3.5 cm as the gestational age advanced from 14 weeks to 35 weeks and six days. After that, it decreased until delivery (r-value = 0.531 (<0.8), p-value <0.001). PT was positively correlated only with birth weight (p-value 0.013) amongst all fetal outcome parameters. Conclusion GA can be determined using PT with the help of regression techniques. PT can be used as a replacement when a particular parameter of the composite growth formula is fallacious. The PT increase rate is a more reliable indicator than the actual PT to predict birth weight.

Epidemiological burden of inborn errors of metabolism in low- and middle-income countries: a systematic review protocol.

OBJECTIVE: This systematic review examines the evidence on the incidence and prevalence of inborn errors of metabolism (IEMs) in low- and middle-income countries (LMICs). INTRODUCTION: IEMs are a set of conditions that can either be inherited or result from spontaneous mutations. Although each condition is rare in isolation, various specific disorders within the IEM group have an estimated global prevalence of 50.9 per 100,000 live births. A precise estimate of the prevalence and incidence of IEM in LMICs can help determine the necessity for extensive newborn screening programs. INCLUSION CRITERIA: This review will cover studies conducted in LMICs, reporting on IEMs in infants and children under the age of 5 years. Studies that calculate birth prevalence and incidence of IEM will be included. Studies that provide information on the causes, clinical characteristics, treatment, case fatality rates, mortality rates, and other outcomes will also be considered. METHODS: The databases to be searched include PubMed, MEDLINE (Ovid), Embase (Ovid), CINAHL (EBSCOhost), Scopus, and gray literature sources. No date or language restrictions will be applied. Our search will encompass analytical and descriptive observational studies, which will be critically appraised by 2 independent reviewers. Data will be extracted using JBI data extraction tools. If sufficient data are available, a meta-analysis will be performed. Alternatively, if data are limited, we will present our findings in narrative format using tables and figures. REVIEW REGISTRATION: PROSPERO CRD42023457421.

The Role of CT Perfusion in Differentiating Benign Versus Malignant Focal Pulmonary Lesions.

BACKGROUND: Contrast-enhanced CT scan is the standard imaging for the characterization and evaluation of focal parenchymal lung lesions. It relies on morphology and enhancement patterns for the characterization of lung lesions. However, there is significant overlap among imaging features of various malignant and benign lesions. Hence, it is often necessary to obtain tissue diagnosis with invasive percutaneous or endoscopic-guided tissue sampling. It is often desirable to have non-invasive techniques that can differentiate malignant and benign lung lesions. CT perfusion is an emerging CT technology that allows functional assessment of tissue vascularity through various parameters and can help in differentiating benign and malignant focal lung lesions. OBJECTIVE: The purpose of this study was to assess the role of the CT perfusion technique in differentiating malignant and benign focal parenchymal lung lesions. MATERIALS AND METHODS: In this prospective observational study, CT perfusion was performed on 41 patients with focal parenchymal lung lesions from December 2020 to June 2022. The four-dimensional range was planned to cover the entire craniocaudal extent of the lesion, followed by a volume perfusion CT (VPCT) of the lesion. A total of 27 dynamic datasets were acquired with a scan interval of 1.5 seconds and a total scan time of 42 seconds. CT perfusion parameters of blood flow (BF), blood volume (BV), and k-trans of the lesion were measured with mathematical algorithms available in the Syngo.via CT perfusion software (Siemens Healthcare, Erlangen, Germany). RESULTS: The median BV in benign lesions was found to be 5.5 mL/100 g, with an interquartile range of 3.3-6.9 and a p-value < 0.001. The median BV in malignant lesions was found to be 11.35 mL/100 g, with an interquartile range of 9.57-13.21 and a p-value ≤ 0.001. The median BF for benign lesions was 45.5 mL/100 g/min, with an interquartile range of 33.8-48.5 and a p-value ≤ 0.001. The median BF for malignant lesion was 61.77 mL/100 g/min, with an interquartile range of 33.8-48.5 and a p-value ≤ 0.001. The median k-trans in the case of benign lesions was found to be 4.2 mL/100 g/min, with an interquartile range of 3.13-6.8 and a p-value ≤ 0.001. The median k-trans in the case of the malignant lesion was found to be 12.05 mL/100g/min, with an interquartile range of 7.20-33.42 and a p-value < 0.001. Our study has also shown BV to have an accuracy of 92.68%, sensitivity of 93.3%, and specificity of 90.01%. CONCLUSION: Our study has shown that CT perfusion values of BV, BF, and k-trans can be used to differentiate between benign and malignant focal lung parenchymal lesions. K-trans is the most sensitive parameter while BV and BF have greater accuracy and specificity.