Molecular detection, risk factors, and phylogenetic analysis of tick-borne pathogens in dogs from northern Vietnam.

In tropical regions, numerous tick-borne pathogens (TBPs) play a crucial role as causative agents of infectious diseases in humans and animals. Recently, the population of companion and pet dogs has significantly increased in Vietnam; however, information on the occurrence of TBPs is still limited. The objectives of this investigation were to determine the occurrence rate, risk factors, and phylogenetic characteristics of TBPs in dogs from northern Vietnam. Of 341 blood samples tested by PCR, the total infection of TBPs was 73.9% (252/341). Babesia vogeli (18SrRNA gene - 30.5%) was detected most frequently in studied dogs followed by Rickettsia spp. (OmpA gene - 27%), Anaplasma platys (groEL gene - 22%), Bartonella spp. (16SrRNA - 18.8%), Mycoplasma haemocanis (16SrRNA - 9.4%) and Hepatozoon canis (18SrRNA gene - 1.2%), respectively. All samples were negative for Ehrlichia canis and Anaplasma phagocytophylum. Co-infection was detected in 31.4% of the samples (107/341) of which, A. platys/Bartonella spp. (34/94,10%), Rickettsia spp./B. vogeli (19/94, 5.6%), and M. haemocanis/B. vogeli (19/94, 5.6%) were recorded as the three most frequent two species of co-infection types. Statistical analysis revealed a significant correlation between TBP infection and several host variables regarding age, breed, and living area in the current study. The recent findings reported herein, for the first time in Vietnam, are essential for local veterinarians when considering the appropriate approaches for diagnosing these diseases. Furthermore, this data can be used to establish control measures for future surveillance and prevention strategies against canine TBPs in Vietnam.

Urban-rural disparities in acceptance of human papillomavirus vaccination among women in Can Tho, Vietnam.

Background: In Vietnam, cervical cancer is a significant public health concern for women. Unfortunately, despite the availability of the HPV vaccine, low vaccination rates persist. Objectives: This study investigates the discrepancy between urban and rural areas in the willingness to receive HPV vaccination with or without fees. Methods: A cross-sectional study was conducted on a sample of 648 women aged between 15 and 49, living in two urban and two rural Vietnamese districts of Can Tho, between May and December 2021. Results: The overall vaccination rate was 4%, with urban women having a higher rate of 4.9% compared to rural women at 3.1%. Among unvaccinated women, those from rural areas expressed a significantly higher desire to receive the free vaccine (91.4%) than urban women (84.4%). However, the intention to vaccinate declined when rural women and urban women were advised to pay the cost (63.4% and 57.1%, respectively). A strong correlation was found between a positive attitude and intention for vaccination, irrespective of its price or free availability. Education and access to information about the HPV vaccine were also identified as the most significant factors influencing the intention to vaccination among urban and rural women. Conclusion: The low HPV vaccination rates among women aged 15-49 living in both urban and rural regions of Vietnam are a notable public health concern. These outcomes emphasize the critical need for effective programs of vaccine laterization, as an introduction to the offer of affordable and accessible HPV vaccines for women in Can Tho, Vietnam.

Patient care during interfacility transport:a narrative review of managing diverse disease states / 世界急诊医学杂志（英文）

BACKGROUND:When critically ill patients require specialized treatment that exceeds the capability of the index hospitals,patients are frequently transferred to a tertiary or quaternary hospital for a higher level of care.Therefore,appropriate and effi cient care for patients during the process of transport between two hospitals(interfacility transfer)is an essential part of patient care.While medical adverse events may occur during the interfacility transfer process,there have not been evidence-based guidelines regarding the equipment or the practice for patient care during transport.METHODS:We conducted searches from the PubMed,Cumulative Index of Nursing and Allied Health(CINAHL),and Scopus databases up to June 2022.Two reviewers independently screened the titles and abstracts for eligibility.Studies that were not in the English language and did not involve critically ill patients were excluded.RESULTS:The search identified 75 articles,and we included 48 studies for our narrative review.Most studies were observational studies.CONCLUSION:The review provided the current evidence-based management of diverse disease states during the interfacility transfer process,such as proning positioning for respiratory failure,extracorporeal membrane oxygenation(ECMO),obstetric emergencies,and hypertensive emergencies(aortic dissection and spontaneous intracranial hemorrhage).

pH-Responsive Metal-Organic Framework Thin Film for Drug Delivery.

In this work, surface-supportive MIL-88B(Fe) was explored as a pH-stimuli thin film to release ibuprofen as a model drug. We used surface plasmon resonance microscopy to study the pH-responsive behaviors of MIL-88B(Fe) film in real time. A dissociation constant of (6.10 ± 0.86) × 10-3 s-1 was measured for the MIL-88B(Fe) film in an acidic condition (pH 6.3), which is about 10 times higher than the dissociation of the same film in a neutral pH condition. MIL-88B(Fe) films are also capable of loading around 6.0 µg/cm2 of ibuprofen, which was measured using a quartz crystal microbalance (QCM). Drug release profiles were compared in both acidic and neutral pH conditions (pH 6.3 and 7.4) using a QCM cell to model the drug release in healthy body systems and those containing inflammatory tissues or cancerous tumors. It was found that the amount of drug released in acidic environments had been significantly higher compared to that in a neutral system within 55 h of testing time. The pH-sensitive chemical bond breaking between Fe3+ and the carboxylate ligands is the leading cause of drug release in acidic conditions. This work exhibits the potential of using MOF thin films as pH-triggered drug delivery systems.

The changing role for extended resections in an era of advanced radiotherapy techniques and novel therapies in gynaecological malignancy.

Pelvic exenteration, first described in 1948 and subsequently refined, may be offered as a last hope of cure to patients with recurrent or locally advanced pelvic tumours, where radiotherapy is not an option. It is a complex, morbid, ultra-radical procedure involving en-bloc resection of the female reproductive organs, lower urinary tract, and a portion of the rectosigmoid. This article discusses the evolution of and current indications for pelvic exenteration in gynaecologic oncology as well as the reasons for its decline: primary and secondary prevention of cervical cancer (the recurrence of which is the most common indication for exenteration); improvements in treatment of cervical, endometrial, vaginal and vulvar cancer in the primary and recurrent setting; and the advent of novel therapies.

Wnt/ß-catenin Signaling Controls Maxillofacial Hyperostosis.

The roles of Wnt/ß-catenin signaling in regulating the morphology and microstructure of craniomaxillofacial (CMF) bones was explored using mice carrying a constitutively active form of ß-catenin in activating Dmp1-expressing cells (e.g., daßcatOt mice). By postnatal day 24, daßcatOt mice exhibited midfacial truncations coupled with maxillary and mandibular hyperostosis that progressively worsened with age. Mechanistic insights into the basis for the hyperostotic facial phenotype were gained through molecular and cellular analyses, which revealed that constitutively activated ß-catenin in Dmp1-expressing cells resulted in an increase in osteoblast number and an increased rate of mineral apposition. An increase in osteoblasts was accompanied by an increase in osteocytes, but they failed to mature. The resulting CMF bone matrix also had an abundance of osteoid, and in locations where compact lamellar bone typically forms, it was replaced by porous, woven bone. The hyperostotic facial phenotype was progressive. These findings identify for the first time a ligand-independent positive feedback loop whereby unrestrained Wnt/ß-catenin signaling results in a CMF phenotype of progressive hyperostosis combined with architecturally abnormal, poorly mineralized matrix that is reminiscent of craniotubular disorders in humans.

Preterm birth and secondhand smoking during pregnancy: A case-control study from Vietnam.

BACKGROUND: The relationship between women who are exposed to secondhand smoke and preterm birth is still controversial. The present study aimed to examine the association between maternal secondhand smoking (SHS) during pregnancy and preterm birth. METHODS: A 1:1 case-control study was conducted at delivery room of The Women's and Children's Hospital of An Giang, Vietnam. A total of 288 cases of preterm birth and 288 controls included in this study. A structured questionnaire in a face-to-face interview was used to assess SHS and potential confounders (maternal age, body mass index, occupation, education level, parity, antenatal care visits, history of preterm birth, prenatal bleeding and preeclampsia/eclampsia). RESULTS: SHS was reported more frequently by women who delivered preterm babies compared with women of term deliveries (67.4% vs. 51.0%; P <0.001). After controlling all potential confounders, multivariable logistic regression analysis showed a relationship between SHS during pregnancy and preterm delivery (adjusted Odds ratio: 1.92; 95% CI 1.31, 2.81). CONCLUSIONS: Our findings suggest that exposure to household tobacco smoke during pregnancy is associated with preterm birth.

Out-of-office blood pressure measurement for the diagnosis of hypertension in pregnancy: Survey of Canadian Obstetric Medicine and Maternal Fetal Medicine specialists.

BACKGROUND: Multiple hypertension guidelines recommend out-of-office measurements for the diagnosis of hypertension in non-pregnant adults, whereas pregnancy guidelines recommend in-office blood pressure measurements. The objective of our study was to determine how Canadian Obstetric Medicine and Maternal Fetal Medicine specialists measure blood pressure in pregnancy. METHODS: An email survey was sent to 69 Canadian Obstetric Medicine and Maternal Fetal Medicine specialists in academic centers across Canada to explore the practice patterns of blood pressure measurement in pregnant women. RESULTS: The response rate was 48%. The majority of respondents (63.6%) preferred office blood pressure measurement for diagnosing hypertension, but relied on home blood pressure readings for ongoing monitoring and management of hypertension during pregnancy (59.4%). The preferred method of out-of-office blood pressure measurement was home monitoring; 24-hour ambulatory blood pressure monitoring was not used due to limited availability and cost. CONCLUSIONS: There is wide practice variation in methods of measuring blood pressure among Canadian specialists managing hypertension in pregnancy.

Enhanced sample filling and discretization in thermoplastic 2D microwell arrays using asymmetric contact angles.

Sample filling and discretization within thermoplastic 2D microwell arrays is investigated toward the development of low cost disposable microfluidics for passive sample discretization. By using a high level of contact angle asymmetry between the filling channel and microwell surfaces, a significant increase in the range of well geometries that can be successfully filled is revealed. The performance of various array designs is characterized numerically and experimentally to assess the impact of contact angle asymmetry and device geometry on sample filling and discretization, resulting in guidelines to ensure robust microwell filling and sample isolation over a wide range of well dimensions. Using the developed design rules, reliable and bubble-free sample filling and discretization is achieved in designs with critical dimensions ranging from 20 µm to 800 µm. The resulting devices are demonstrated for discretized nucleic acid amplification by performing loop-mediated isothermal amplification for the detection of the mecA gene associated with methicillin-resistant Staphylococcus aureus.

An Efficient Procedure for the Synthesis of 21-Acetoxypregna-1,4,9(11),16- tetraene-3,20-dione.

BACKGROUND: Halogenated corticosteroids are widely used in medicine, and the global need of these steroidal APIs is estimated to be 40 - 70 tons, annually. Vietnam currently imports the pharmaceutical compounds up to 90%, in particular 100% of steroidal drugs. Currently, industrial production is based on the chemical syntheses of corticosteroids from either 16- dehydropregnenolone acetate (obtained from diosgenin) or androstenedione (obtained from phytosterol). The development of shorter synthetic schemes and more economically feasible technologies is of great significance. Introduction of 1(2)-double bond at the final stages of the corticosteroids synthesis results inpoor yield. 21-Acetoxypregna-1,4,9(11),16-tetraene-3,20-dione (tetraene acetate) is a key intermediate in the synthesis of highly active halogenated corticosteroids such as dexamethasone and other halogenated corticosteroids. 21-acetoxypregna-1,4,9(11),16- tetraene-3,20-dione is a key intermediate in the synthesis of dexamethasone from the readily available and cheap 9α-hydroxyandrost-4-ene-3,17-dione. OBJECTIVE: The purpose of this study was the development of an efficient and shorter procedure for the synthesis of 21-acetoxypregna-1,4,9(11),16-tetraene-3,20-dione from 9α-hydroxyandrostenedione, which is a product of a bio-oxidative degradation of the side chain of phytosterols. METHODS: Pregnane side chain was constructed using cyanohydrin method. For 1(2)- dehydrogenation, selene dioxide was applied for the introduction of Δ1(2)-double bond. Other stages of the synthesis were epimerization, Stork's iodination procedure and dehydration. RESULT: 21-Acetoxypregna-1,4,9(11),16-tetraene-3,20-dione was prepared from 9α- hydroxyandrostenedione in yield more than 46%. CONCLUSION: An efficient and practically feasible procedure for the synthesis of 21-acetoxypregna- 1,4,9(11),16-tetraene-3,20-dione from 9α-hydroxyandrostenedione, a key intermediate for the synthesis of 9-haloidated corticoids, has been developed. The procedure can be applied for the production of value-added 9-haloidated corticoids.

Parenting Teamwork: The Impact of a Fathering Intervention on Mothers and Infants in Vietnam.

A multifaceted, relationally focused intervention involving group and individual pre- and postnatal counseling, print resources, and community resources encouraged 390 fathers of newborn infants in Vietnam to responsively support mothers and work with them as a parenting team. Both partners completed questionnaires prebirth and 1-, 4-, and 9-months postbirth on measures of breastfeeding support, exclusive breastfeeding duration, relationship quality, and infant development. Compared to 412 comparison group couples, intervention couples evidenced greater father support, especially in terms of helping and responsiveness to the mother's needs. This support predicted longer exclusive breastfeeding duration, improved relationship quality, and higher levels of infant development at 9 months. Sensitively working together with mothers as a coordinated team enhanced couple's relationship functioning and improved children's developmental outcomes.

Validation of the BIOCHIP test for the diagnosis of bullous pemphigoid, pemphigus vulgaris and pemphigus foliaceus.

BACKGROUND: The BIOCHIP is a novel multiplex indirect immunofluorescence technique used in the serological diagnosis of bullous pemphigoid and pemphigus. The BIOCHIP method combines the screening of autoantibodies and target antigen-specific substrates in a single miniature incubation field. OBJECTIVE: To evaluate the diagnostic accuracy of the new immunofluorescence BIOCHIP multiplex tool in pemphigus and bullous pemphigoid. METHODS: For the validation of the BIOCHIP, sera from patients with BP (n = 38), PF (n = 8) and pemphigus vulgaris (PV) (n = 23) were used. In addition, sera from disease control patients (n = 63) and healthy volunteers (n = 39) were used. The multiplex BIOCHIP and direct immunofluorescence (DIF) were performed for all BP, PF and PV patients. Additional indirect immunofluorescence (IIF) was performed on patients with BP, and ELISA was performed on patients with pemphigus. RESULTS: The BIOCHIP mosaic showed a sensitivity of 86.8% and specificity of 85% for BP180 or BP230 being positive in BP. It demonstrated a sensitivity of 75% and specificity of 97.7% for Dsg1 in PF. The BIOCHIP was found to have a sensitivity of 60.9% and specificity of 73.6% for Dsg3 in PV. CONCLUSION: The BIOCHIP mosaic-based immunofluorescence test is potentially a simple, time and effort saving test that can aid in the diagnosis and screening of BP, PV and PF. However, there is potential for interpretation bias and a learning curve that needs to be taken into consideration.

Design, Synthesis and Biological Evaluation of Novel N-hydroxyheptanamides Incorporating 6-hydroxy-2-methylquinazolin-4(3H)-ones as Histone Deacetylase Inhibitors and Cytotoxic Agents.

BACKGROUND: Target-based approach to drug discovery currently attracts a great deal of interest from medicinal chemists in anticancer drug discovery and development worldwide, and Histone Deacetylase (HDAC) inhibitors represent an extensive class of targeted anti-cancer agents. Among the most explored structure moieties, hydroxybenzamides and hydroxypropenamides have been demonstrated to have potential HDAC inhibitory effects. Several compounds of these structural classes have been approved for clinical uses to treat different types of cancer, such as vorinostat and belinostat. AIMS: This study aims at developing novel HDAC inhibitors bearing quinazolinone scaffolds with potential cytotoxicity against different cancer cell lines. METHODS: A series of novel N-hydroxyheptanamides incorporating 6-hydroxy-2 methylquinazolin-4(3H)-ones (14a-m) was designed, synthesized and evaluated for HDAC inhibitory potency as well as cytotoxicity against three human cancer cell lines, including HepG-2 (liver cancer), MCF-7 (breast cancer) and SKLu-1 (lung cancer). Molecular simulations were finally carried out to gain more insight into the structure-activity relationships. ADME-T predictions for selected compounds were also performed to predict some important features contributing to the absorption profile of the present hydroxamic derivatives. RESULTS: It was found that the N-hydroxyheptanamide 14i and 14j were the most potent, both in terms of HDAC inhibition and cytotoxicity. These compounds displayed up to 21-71-fold more potent than SAHA (suberoylanilide hydroxamic acid, vorinostat) in terms of cytotoxicity, and strong inhibition against the whole cell HDAC enzymes with IC50 values of 7.07-9.24µM. Docking experiments on HDAC2 isozyme using Autodock Vina showed all compounds bound to HDAC2 with relatively higher affinities (from -7.02 to -11.23 kcal/mol) compared to SAHA (-7.4 kcal/mol). It was also found in this research that most of the target compounds seemed to be more cytotoxic toward breast cancer cells (MCF-7) than liver (HepG2), and lung (SKLu-1) cancer cells.

Respiratory dysfunction in myotonic dystrophy type 1: A systematic review.

Myotonic dystrophy type 1 (DM1) is one of the most common muscular dystrophies in adults. This review summarises the current literature regarding the natural history of respiratory dysfunction in DM1, the role of central respiratory drive and peripheral respiratory muscle involvement and its significance in respiratory function, and investigates the relationship between genetics (CTG repeat length) and respiratory dysfunction. The review included all articles that reported spirometry on 10 or more myotonic dystrophy patients. The final review included 55 articles between 1964 and 2017. The major conclusions of this review were (1) confirmation of the current consensus that respiratory dysfunction, predominantly a restrictive ventilatory pattern, is common in myotonic dystrophy and is associated with alveolar hypoventilation, chronic hypercapnia, and sleep disturbance in the form of sleep apnoea and sleep related disordered breathing; (2) contrary to commonly held belief, there is no consensus in the literature regarding the relationship between CTG repeat length and severity of respiratory dysfunction and a relationship has not been established; (3) the natural history and time-course of respiratory functional decline is very poorly understood in the current literature; (4) there is a consensus that there is a significant involvement of central respiratory drive in this alveolar hypoventilation however the current literature does not identify the mechanism for this.

Epithelial barrier dysfunctions in atopic dermatitis: a skin-gut-lung model linking microbiome alteration and immune dysregulation.

BACKGROUND: Atopic dermatitis is a systemic disorder characterized by abnormal barrier function across multiple organ sites. Causes of epidermal barrier breakdown are complex and driven by a combination of structural, genetic, environmental and immunological factors. In addition, alteration in microflora diversity can influence disease severity, duration, and response to treatment. Clinically, atopic dermatitis can progress from skin disease to food allergy, allergic rhinitis, and later asthma, a phenomenon commonly known as the atopic march. The mechanism by which atopic dermatitis progresses towards gastrointestinal or airway disease remains to be elucidated. OBJECTIVES: This review addresses how epithelial dysfunction linking microbiome alteration and immune dysregulation can predispose to the development of the atopic march. METHODS: A literature search was conducted using the PubMed database for relevant articles with the keywords 'atopic dermatitis', 'epithelial barrier', 'skin', 'gut', 'lung', 'microbiome' and 'immune dysregulation'. RESULTS: Initial disruption in the skin epidermal barrier permits allergen sensitization and colonization by pathogens. This induces a T helper 2 inflammatory response and a thymic stromal lymphopoietin-mediated pathway that further promotes barrier breakdown at distant sites, including the intestinal and respiratory tract. CONCLUSIONS: As there are no immediate cures for food allergy or asthma, early intervention aimed at protecting the skin barrier and effective control of local and systemic inflammation may improve long-term outcomes and reduce allergen sensitization in the airway and gut.

Proton pump inhibitor and histamine-2 receptor antagonist use and risk of liver cancer in two population-based studies.

BACKGROUND: Proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) are commonly used. PPIs have been shown to promote liver cancer in rats; however, only one study has examined the association in humans. AIMS: To investigate PPIs and H2RAs and risk of primary liver cancer in two large independent study populations. METHODS: We conducted a nested case-control study within the Primary Care Clinical Informatics Unit (PCCIU) database in which up to five controls were matched to cases with primary liver cancer, recorded by General Practitioners. Odds ratios (ORs) and 95% confidence intervals (95% CIs) for associations with prescribed PPIs and H2RAs were calculated using conditional logistic regression. We also conducted a prospective cohort study within the UK Biobank using self-reported medication use and cancer-registry recorded primary liver cancer. Hazard ratios (HRs) and 95% CIs were calculated using Cox regression. RESULTS: In the PCCIU case-control analysis, 434 liver cancer cases were matched to 2103 controls. In the UK Biobank cohort, 182 of 475 768 participants developed liver cancer. In both, ever use of PPIs was associated with increased liver cancer risk (adjusted OR 1.80, 95% CI 1.34, 2.41 and adjusted HR 1.99, 95% CI 1.34, 2.94 respectively). There was little evidence of association with H2RA use (adjusted OR 1.21, 95% CI 0.84, 1.76 and adjusted HR 1.70, 95% CI 0.82, 3.53 respectively). CONCLUSIONS: We found some evidence that PPI use was associated with liver cancer. Whether this association is causal or reflects residual confounding or reverse causation requires additional research.

Measuring patient-reported outcomes to improve cancer care in Canada: an analysis of provincial survey data.

Patient-reported outcomes measures (proms) are an important component of the shift from disease-centred to person-centred care. In oncology, proms describe the effects of cancer and its treatment from the patient perspective and ideally enable patients to communicate to their providers the physical symptoms and psychosocial concerns that are most relevant to them. The Edmonton Symptom Assessment System-revised (esas-r) is a commonly used and validated tool in Canada to assess symptoms related to cancer. Here, we describe the extent to which patient-reported outcome programs have been implemented in Canada and the severity of symptoms causing distress for patients with cancer. As of April 2017, 8 of 10 provinces had implemented the esas-r to assess patient-reported outcomes. Data capture methods, the proportion of cancer treatment sites that have implemented the esas-r, and the time and frequency of screening vary from province to province. From October 2016 to March 2017 in the 8 reporting provinces, 88.0% of cancer patients were screened for symptoms. Of patients who reported having symptoms, 44.3% reported depression, with 15.5% reporting moderate-to-high levels; 50.0% reported pain, with 18.6% reporting moderate-to-high levels; 56.2% reported anxiety, with 20.4% reporting moderate-to-high levels; and 75.1% reported fatigue, with 34.4% reporting moderate-to-high levels. There are some notable areas in which the implementation of proms could be improved in Canada. Findings point to a need to increase the number of cancer treatment sites that screen all patients for symptoms; to standardize when and how frequently patients are screened across the country; to screen patients for symptoms during all phases of their cancer journey, not just during treatment; and to assess whether giving cancer care providers real-time patient-reported outcomes data has led to appropriate interventions that reduce the symptom burden and improve patient outcomes. Continued measurement and reporting at the system level will allow for a better understanding of progress in proms activity over time and of the areas in which targeted quality improvement efforts could ensure that patient symptoms and concerns are being addressed.

Mobilization of iron from ferritin: new steps and details.

Much evidence indicates that iron stored in ferritin is mobilized through protein degradation in lysosomes, but concerns about this process have lingered, and the mechanistic details of its aspects are lacking. In the studies presented here, 59Fe-labeled ferritin was induced by preloading hepatic (HepG2) cells with radiolabeled Fe. Placing these cells in a medium containing desferrioxamine resulted in the loss of ferritin-59Fe, but adding high concentrations of reducing agents or modulating the internal GSH concentration failed to alter the rates of ferritin-59Fe release. Confocal microscopy showed that Fe deprivation increased the movement of ferritin into lysosomes and hyperaccumulation was observed when lysosomal proteolysis was inhibited. It also resulted in the rapid movement of DMT1 to lysosomes, which was inhibited by bafilomycin. Ferrihydrite crystals isolated from purified rat liver/spleen ferritin were solubilized at pH 5 and 7 by GSH, ascorbate, citrate and lysosomal fluids obtained from livers and J774a.1 macrophages. The inhibition of DMT1/Nramp2 and siRNA knockdown of Nramp1 each reduced the transfer of 59Fe from lysosomes to the cytosol; and hepatocyte-specific knockout of DMT1 in mice prevented the release of Fe from the liver responding to EPO treatment, but did not inhibit lysosomal ferritin degradation. We conclude that ferritin-Fe mobilization does not occur through changes in cellular concentrations of reducing/chelating agents but by the coordinated movement of ferritin and DMT1 to lysosomes, where the ferrihydrite crystals exposed by ferritin degradation dissolve in the lysosomal fluid, and the reduced iron is transported back to the cytosol via DMT1 in hepatocytes, and by both DMT1 and Nramp1 in macrophages, prior to release into the blood or storage in ferritin.