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.

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.

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.

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.

Infantile fetiform abdominal mass: Teratoma or fetus in fetu? A case report with insights into radiological diagnosis and surgical management.

Fetus-in-fetu (FIF) is a rare congenital anomaly in which a malformed parasitic twin develops within the body of a live fetus or child. Abdominal teratoma, a type of germ cell tumor, can be a great imaging mimicker of FIF and vice-versa, as they both can present as a heterogeneous mass with calcifications and a fat component. Radiological differentiation of these 2 entities should be made because of the difference in surgical planning and treatment options. Features such as visualization of distinct bony vertebral elements and encysted cystic components are the specific features of Fetus in fetu [1]. In contrast, the presence of elevated serum markers can help diagnose teratoma. Here, we report a case of a 5-month-old girl presented with progressive distension of the upper abdomen for the last 2 months, noticed by her mother. Her initial imaging with abdominal X-ray and ultrasonography showed the presence of a large heterogenous solid-cystic mass in the upper abdomen with large elongated calcifications. A provisional diagnosis of teratoma vs FIF was considered. CECT abdomen showed clear identification of osseous structures of the axial and appendicular skeleton within a fat density mass, along with an encapsulated cystic component, strongly suggestive of FIF. Her serum tumor markers were within normal limits. The final diagnosis of FIF was confirmed on Laparotomy and postoperative specimens.

Inductively coupled, transmit-receive coils for proton MRI and X-nucleus MRI/MRS in small animals.

We report several inductively coupled RF coil designs that are very easy to construct, produce high signal-to-noise ratio (SNR) and high spatial resolution while accommodating life support, anesthesia and monitoring in small animals. Inductively coupled surface coils were designed for hyperpolarized 13 C MR spectroscopic imaging (MRSI) of mouse brain, with emphases on the simplicity of the circuit design, ease of use, whole-brain coverage, and high SNR. The simplest form was a resonant loop designed to crown the mouse head for a snug fit to achieve full coverage of the brain with high sensitivity when inductively coupled to a broadband pick-up coil. Here, we demonstrated the coil's performance in hyperpolarized 13 C MRSI of a normal mouse and a glioblastoma mouse model at 4.7 T. High SNR exceeding 70:1 was obtained in the brain with good spatial resolution (1.53 mm × 1.53 mm). Similar inductively coupled loop for other X-nuclei can be made very easily in a few minutes and achieve high performance, as demonstrated in 31 P spectroscopy. Similar design concept was expanded to splitable, inductively coupled volume coils for high-resolution proton MRI of marmoset at 3T and 9.4T, to easily accommodate head restraint, vital-sign monitoring, and anesthesia delivery.

A marmoset brain cell census reveals regional specialization of cellular identities.

The mammalian brain is composed of many brain structures, each with its own ontogenetic and developmental history. We used single-nucleus RNA sequencing to sample over 2.4 million brain cells across 18 locations in the common marmoset, a New World monkey primed for genetic engineering, and examined gene expression patterns of cell types within and across brain structures. The adult transcriptomic identity of most neuronal types is shaped more by developmental origin than by neurotransmitter signaling repertoire. Quantitative mapping of GABAergic types with single-molecule FISH (smFISH) reveals that interneurons in the striatum and neocortex follow distinct spatial principles, and that lateral prefrontal and other higher-order cortical association areas are distinguished by high proportions of VIP+ neurons. We use cell type-specific enhancers to drive AAV-GFP and reconstruct the morphologies of molecularly resolved interneuron types in neocortex and striatum. Our analyses highlight how lineage, local context, and functional class contribute to the transcriptional identity and biodistribution of primate brain cell types.

Phytoremediation technologies and their mechanism for removal of heavy metal from contaminated soil: An approach for a sustainable environment.

The contamination of soils with heavy metals and its associated hazardous effects are a thrust area of today's research. Rapid industrialization, emissions from automobiles, agricultural inputs, improper disposal of waste, etc., are the major causes of soil contamination with heavy metals. These contaminants not only contaminate soil but also groundwater, reducing agricultural land and hence food quality. These contaminants enter the food chain and have a severe effect on human health. It is important to remove these contaminants from the soil. Various economic and ecological strategies are required to restore the soils contaminated with heavy metals. Phytoremediation is an emerging technology that is non-invasive, cost-effective, and aesthetically pleasing. Many metal-binding proteins (MBPs) of the plants are significantly involved in the phytoremediation of heavy metals; the MBPs include metallothioneins; phytochelatins; metalloenzymes; metal-activated enzymes; and many metal storage proteins, carrier proteins, and channel proteins. Plants are genetically modified to enhance their phytoremediation capacity. In Arabidopsis, the expression of the mercuric ion-binding protein in Bacillus megaterium improves the metal accumulation capacity. The phytoremediation efficiency of plants is also enhanced when assisted with microorganisms, biochar, and/or chemicals. Removing heavy metals from agricultural land without challenging food security is almost impossible. As a result, crop selections with the ability to sequester heavy metals and provide food security are in high demand. This paper summarizes the role of plant proteins and plant-microbe interaction in remediating soils contaminated with heavy metals. Biotechnological approaches or genetic engineering can also be used to tackle the problem of heavy metal contamination.

Isolated primary hydatid cyst of the pancreas: Management challenges of a cystic masquerade.

Abdominal hydatid cyst disease mostly involves the liver. Involvement of the pancreas as an isolated primary organ is rare accounting for < 2% of all systemic echinococcosis cases. It mostly involves the head of the pancreas. Symptoms depend on the location, size, and associated complications; therefore, it can have varied presentations including acute pancreatitis. On imaging, it can mimic other common pancreatic cystic lesions like pseudocyst or cystic neoplasm. Accurate preoperative diagnosis is usually difficult and requires a very high index of suspicion even in endemic areas. Herein, a case of primary isolated hydatid cyst of the pancreas that was initially diagnosed and managed as acute pancreatic pseudocyst is reported.

Delayed complication due to retained contrast following augmented pressure distal loop colostogram in anorectal malformation.

Augmented-pressure distal loop colostogram (APDC) is the most important diagnostic investigation to delineate the detailed anatomy to plan the reparative management of anorectal malformations. APDC is generally considered safe, with a very low complication rate. Herein, we present an unreported complication of APDC, manifesting as acute abdomen, due to retained contrast in distal loop. The patient was managed with evacuation of retained contrast from distal loop. We recommend evacuating the contrast from the distal loop following APDC.

AAV capsid variants with brain-wide transgene expression and decreased liver targeting after intravenous delivery in mouse and marmoset.

Genetic intervention is increasingly being explored as a therapeutic option for debilitating disorders of the central nervous system. The safety and efficacy of gene therapies rely upon expressing a transgene in affected cells while minimizing off-target expression. Here we show organ-specific targeting of adeno-associated virus (AAV) capsids after intravenous delivery, which we achieved by employing a Cre-transgenic-based screening platform and sequential engineering of AAV-PHP.eB between the surface-exposed AA452 and AA460 of VP3. From this selection, we identified capsid variants that were enriched in the brain and targeted away from the liver in C57BL/6J mice. This tropism extends to marmoset (Callithrix jacchus), enabling robust, non-invasive gene delivery to the marmoset brain after intravenous administration. Notably, the capsids identified result in distinct transgene expression profiles within the brain, with one exhibiting high specificity to neurons. The ability to cross the blood-brain barrier with neuronal specificity in rodents and non-human primates enables new avenues for basic research and therapeutic possibilities unattainable with naturally occurring serotypes.

Hemodynamic molecular imaging of tumor-associated enzyme activity in the living brain.

Molecular imaging could have great utility for detecting, classifying, and guiding treatment of brain disorders, but existing probes offer limited capability for assessing relevant physiological parameters. Here, we describe a potent approach for noninvasive mapping of cancer-associated enzyme activity using a molecular sensor that acts on the vasculature, providing a diagnostic readout via local changes in hemodynamic image contrast. The sensor is targeted at the fibroblast activation protein (FAP), an extracellular dipeptidase and clinically relevant biomarker of brain tumor biology. Optimal FAP sensor variants were identified by screening a series of prototypes for responsiveness in a cell-based bioassay. The best variant was then applied for quantitative neuroimaging of FAP activity in rats, where it reveals nanomolar-scale FAP expression by xenografted cells. The activated probe also induces robust hemodynamic contrast in nonhuman primate brain. This work thus demonstrates a potentially translatable strategy for ultrasensitive functional imaging of molecular targets in neuromedicine.

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.

Barley Melanoidins: Key Dietary Compounds With Potential Health Benefits.

This paper is a review of the potential health benefits of barley melanoidins. Food melanoidins are still rather understudied, despite their potential antioxidant, antimicrobial, and prebiotic properties. Free radicals are villainous substances in humans produced as metabolic byproducts and causing cancers and cardiovascular diseases, and the melanoidins alleviate the effects of these free radicals. Malt is produced from cereal grains such as barley, wheat, and maize, and barley is predominantly used in beer production. Beer (alcoholic and non-alcoholic) is a widely consumed beverage worldwide and a good source of dietary melanoidins, which enhance the beers' flavor, texture, and sensorial properties. Melanoidins, the final products of the Maillard reaction, are produced at different stages during the brewing process. Beer melanoidins protect the cells from oxidative damage of DNA. The high reducing capacity of melanoidins can induce hydroxyl radicals from H2O2 in the presence of ferric ion (Fe3+). Melanoidins inhibit lipid peroxidation during digestion due to their chelating metal property. However, lower digestibility of melanoidins leads to less availability to the organisms but is considered to function as dietary fiber that can be metabolized by the lower gut microbiota and possibly incur prebiotic properties. Melanoidins promote the growth of Lactobacilli and Bifidobacteria in the gastrointestinal tract, preventing the colonization of potential pathogens. Barley is already popular through beer production and increasingly as a functional food. Considering this economic and industrial importance, more research to explore the chemical properties of barley melanoidins and corresponding health benefits as barley is warranted.

Spinal Eumycetoma: A Rare Cause of Lumbar Canal Stenosis and Significance of "Dot in Circle".

Mycetoma is a chronic granulomatous disease that is more common in tropical regions with predominant involvement of foot. Spinal mycetoma presenting as lumbar canal stenosis is extremely rare. We hereby present a case of fungal eumycetoma of vertebral column in a 42-year-old male who presented with chronic progressive low back pain and features of lumbar canal stenosis without any skin swelling or discharging sinuses. The "dot-in-circle" sign, a highly specific magnetic resonance imaging (MRI) and ultrasonography (USG) sign of mycetoma has been described in the literature as a pathognomonic feature of mycetoma involving the musculoskeletal system. We describe the importance of characteristic imaging features with dot in circle sign in the diagnosis of eumycetoma of lumbar spine.

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.

Viral manipulation of functionally distinct interneurons in mice, non-human primates and humans.

Recent success in identifying gene-regulatory elements in the context of recombinant adeno-associated virus vectors has enabled cell-type-restricted gene expression. However, within the cerebral cortex these tools are largely limited to broad classes of neurons. To overcome this limitation, we developed a strategy that led to the identification of multiple new enhancers to target functionally distinct neuronal subtypes. By investigating the regulatory landscape of the disease gene Scn1a, we discovered enhancers selective for parvalbumin (PV) and vasoactive intestinal peptide-expressing interneurons. Demonstrating the functional utility of these elements, we show that the PV-specific enhancer allowed for the selective targeting and manipulation of these neurons across vertebrate species, including humans. Finally, we demonstrate that our selection method is generalizable and characterizes additional PV-specific enhancers with exquisite specificity within distinct brain regions. Altogether, these viral tools can be used for cell-type-specific circuit manipulation and hold considerable promise for use in therapeutic interventions.

Analysis of stones formed in the human gall bladder and kidney using advanced spectroscopic techniques.

Stone diseases (gallstones and kidney stones) are extremely painful and often cause death. The prime aim of biomedical research in this area has been determination of factors resulting in stone formation inside the gallbladder and urinary tract. Many theories have been put forward to explain the mechanism of stone formation and their growth; however, their complete cycle of pathogenesis is still under debate. Several factors are responsible for stone formation; however, much emphasis is placed on the determination of elemental and molecular composition of the stones. In the present review article, we describe different kinds of spectroscopic techniques such as Fourier transform infrared spectroscopy (FTIR), X-ray fluorescence (XRF) spectroscopy, time-of-flight secondary ion mass spectrometry (TOF-SIMS), and laser-induced breakdown spectroscopy (LIBS) and highlight their use in the analysis of stone diseases. We have summarized work done on gallstones and kidney stones using these advanced techniques particularly over the last 10 years. We have also briefly elaborated the basics of stone formations inside the human body and their complications for a better understanding of the subject.