Impact of COVID-19 on the Utilization of Maternal and Child Health Services at a Regional Referral Hospital in Kenya.

Background and Objective: Pandemics, like COVID-19, disrupt healthcare, potentially reversing progress in various disease areas. The impact on maternal and child health (MCH) services in Kenya during the pandemic is yet to be determined. Recognizing this impact is crucial for formulating policies and programs that minimize disruptions in reproductive health services during future health crises. The purpose of this study was to determine the effect of COVID-19 on the uptake of MCH services at Thika Level V Hospital, a regional referral hospital in Kenya. Methods: In this cross-sectional mixed methods study, we reviewed antenatal clinic (ANC), MCH, and family planning (FP) registers for data on the uptake of the various services during the COVID-19 pandemic (July to October 2020) compared to a year before the COVID-19 pandemic (July to October 2019). MCH clients (N = 60) and healthcare workers (N = 19) were interviewed about the impact of the pandemic on MCH services at the hospital. Differences in clinic attendance before and during the pandemic were compared using the student t-test. Thematic analysis was conducted on the interview responses. Results: The number of MCH/FP clients dropped from 12,915 pre-pandemic to 7,429 during the pandemic. Significant differences were noted in ANC revisits (p = 0.026) and those completing the World Health Organization recommended minimum of four ANC visits (p<0.001) during the COVID-19 pandemic. The number of revisits at the child welfare clinic was also significantly lower (p = 0.004) during the COVID-19 lockdown period. MCH clients stated that the decline in the uptake of MCH services was attributable to the fear of contracting disease, financial difficulties, and strain on the healthcare workforce. Conclusion and Global Health Implications: This study found a decline in access to MCH/FP services during the COVID-19 crisis with the potential to reverse gains made in securing the safety of the pregnant mother and unborn baby.

A survey and taxonomy of 2.5D approaches for lung segmentation and nodule detection in CT images.

CAD systems for lung cancer diagnosis and detection can significantly offer unbiased, infatiguable diagnostics with minimal variance, decreasing the mortality rate and the five-year survival rate. Lung segmentation and lung nodule detection are critical steps in the lung cancer CAD system pipeline. Literature on lung segmentation and lung nodule detection mostly comprises techniques that process 3-D volumes or 2-D slices and surveys. However, surveys that highlight 2.5D techniques for lung segmentation and lung nodule detection still need to be included. This paper presents a background and discussion on 2.5D methods to fill this gap. Further, this paper also gives a taxonomy of 2.5D approaches and a detailed description of the 2.5D approaches. Based on the taxonomy, various 2.5D techniques for lung segmentation and lung nodule detection are clustered into these 2.5D approaches, which is followed by possible future work in this direction.

Optical Flow Methods for Lung Nodule Segmentation on LIDC-IDRI Images.

Lung nodule segmentation is an essential step in any CAD system for lung cancer detection and diagnosis. Traditional approaches for image segmentation are mainly morphology based or intensity based. Motion-based segmentation techniques tend to use the temporal information along with the morphology and intensity information to perform segmentation of regions of interest in videos. CT scans comprise of a sequence of dicom 2-D image slices similar to videos which also comprise of a sequence of image frames ordered on a timeline. In this work, Farneback, Horn-Schunck and Lucas-Kanade optical flow methods have been used for processing the dicom slices. The novelty of this work lies in the usage of optical flow methods, generally used in motion-based segmentation tasks, for the segmentation of nodules from CT images. Since thin-sliced CT scans are the imaging modality considered, they closely approximate the motion videos and are the primary motivation for using optical flow for lung nodule segmentation. This paper also provides a detailed comparative analysis and validates the effectiveness of using optical flow methods for segmentation. Finally, we propose methods to further improve the efficiency of segmentation using optical flow methods on CT scans.

In vivo development of heterogeneous glycopeptide-intermediate Staphylococcus aureus (hGISA), GISA and daptomycin resistance in a patient with meticillin-resistant S. aureus endocarditis.

We report a patient who developed a meticillin-resistant Staphylococcus aureus (MRSA) central venous catheter infection complicated by infective endocarditis. The patient was initially treated with glycopeptides, which led to the development of heterogeneous glycopeptide resistance, the detection of which required the use of a macro Etest screening test. Subsequently, the causative strain, confirmed by PFGE as a UK epidemic MRSA-15, was treated with daptomycin, and again resistance developed in vivo. The development in vivo of resistance to both these agents suggests that the resistance mechanisms may be associated. We suggest that the clinician managing MRSA infection should anticipate daptomycin resistance when reduced glycopeptide susceptibility is detected.

The clinical effectiveness of central venous catheters treated with anti-infective agents in preventing catheter-related bloodstream infections: a systematic review.

OBJECTIVES: To assess the clinical effectiveness of central venous catheters (CVCs) treated with anti-infective agents (AI-CVCs) in preventing catheter-related bloodstream infections (CRBSI). DATA SOURCES: MEDLINE (OVID), EMBASE, SCI//Web of Science, SCI/ISI Proceedings, and the Cochrane Library. STUDY SELECTION: A systematic review of the literature was conducted using internationally recognized methodology. All included articles were reports of randomized controlled trials comparing the clinical effectiveness of CVCs treated with AI-CVCs with either standard CVCs or another anti-infective treated catheter. Articles requiring in-house preparation of catheters or that only reported interim data were excluded. DATA EXTRACTION: Data extraction was carried out independently and crosschecked by two reviewers using a pretested data extraction form. DATA SYNTHESIS: Meta-analyses were conducted to assess the effectiveness of AI-CVCs in preventing CRBSI, compared with standard CVCs. Results are presented in forest plots with 95% confidence intervals. RESULTS: Thirty-eight randomized controlled trials met the inclusion criteria. Methodologic quality was generally poor. Meta-analyses of data from 27 trials assessing CRBSI showed a strong treatment effect in favor of AI-CVCs (odds ratio 0.49 (95% confidence interval 0.37-0.64) fixed effects, test for heterogeneity, chi-square = 28.78, df = 26, p = 0.321, I = 9.7). Results subgrouped by the different types of anti-infective treatments generally demonstrated treatment effects favoring the treated catheters. Sensitivity analyses investigating the effects of methodologic differences showed no differences to the overall conclusions of the primary analysis. CONCLUSION: AI-CVCs appear to be effective in reducing CRBSI compared with standard CVCs. However, it is important to establish whether this effect remains in settings where infection-prevention bundles of care are established as routine practice. This review does not address this question and further research is required.

Robust B cell immunity but impaired T cell proliferation in the absence of CD134 (OX40).

CD134 (OX40) is a member of the TNF receptor family that is expressed on activated T lymphocytes. T cells from mice that lack expression of CD134 made strong responses to a range of challenges, but they showed impaired proliferation in response to direct stimulation through the TCR with monoclonal anti-CD3epsilon Ab. CD134-deficient mice controlled infection with Leishmania major, Nippostrongylus brasiliensis, and Theiler's murine encephalomyelitis virus, and they made overtly normal Ab responses to a variety of antigens. Thus, CD134 is not essential for many T cell responses in vivo, nor is it required for the provision of help to B cells. Nonetheless, a subtle role in the regulation of T cell reactivity is suggested by the effect of CD134 deficiency on in vitro T cell responses.

A novel five-transmembrane hematopoietic stem cell antigen: isolation, characterization, and molecular cloning.

Phenotypic analysis of hematopoietic stem and progenitor cells (HSCs) has been an invaluable tool in defining the biology of stem cell populations. We have recently described the production of AC133, a monoclonal antibody (MoAb) that binds to a novel cell surface antigen present on a CD34(bright) subset of human HSCs. This antigen is a glycosylated protein with a molecular weight of 120 kD. Here, we report the molecular cloning of a cDNA encoding this antigen and show that it does not share homology with any previously described hematopoietic or other cell surface antigen(s). The AC133 polypeptide has a predicted size of 97 kD and contains five-transmembrane (5-TM) domains with an extracellular N-terminus and a cytoplasmic C-terminus. Whereas the expression of tetraspan (4-TM) and 7-TM molecules is well documented on mature and immature hematopoietic cells and leukocytes, this 5-TM type of structure containing two large (255-amino acid [aa] and 290-aa) extracellular loops is unique and does not share sequence homology with any known multi-TM family members. Expression of this protein appears limited to bone marrow in normal tissue by immunohistochemical staining; however, Northern analysis suggests that the mRNA transcript is present in a variety of tissues such as the kidney, pancreas, placenta, and fetal liver. The AC133 antigen is also expressed on subsets of CD34+ leukemias, suggesting that it may be an important early marker for HSCs, as well as the first described member of a new class of TM receptors.

Selective depletion of myelin-reactive T cells with the anti-OX-40 antibody ameliorates autoimmune encephalomyelitis.

The OX-40 protein was selectively upregulated on encephalitogenic myelin basic protein (MBP)-specific T cells at the site of inflammation during the onset of experimental autoimmune encephalomyelitis (EAE). An OX-40 immunotoxin was used to target and eliminate MBP-specific T cells within the central nervous system without affecting peripheral T cells. When injected in vivo, the OX-40 immunotoxin bound exclusively to myelin-reactive T cells isolated from the CNS, which resulted in amelioration of EAE. Expression of the human OX-40 antigen was also found in peripheral blood of patients with acute graft-versus-host disease and the synovia of patients with rheumatoid arthritis during active disease. The unique expression of the OX-40 molecule may provide a novel therapeutic strategy for eliminating autoreactive CD4+T cells that does not require prior knowledge of the pathogenic autoantigen.

Characterization of the epitope recognized by a mAb that reacts differentially with murine suppressor T cells.

Although reliable antibodies are available that distinguish human suppressor T (Ts) cells from CTL and other T cells, few are available for murine Ts cells. We have developed a mAb (984D4.6.5) that, in the presence of complement, depletes alloantigen-specific Ts cells but not CTL. This antibody recognizes activated Ts cells but not their precursors. In these studies, flow cytometric analysis demonstrates that 984D4.6.5 reacts with several Ts cell hybridomas, cloned Ts cell lines and WEHI-3 (a myelomonocytic tumor cell line). Reactivity was not detected with BW5147, Th cell hybridomas, cloned Th cells, CTL lines and hybridomas, B cell lines, thymocytes, splenocytes, bone marrow cells nor a variety of tumor cells. Among 984D4.6.5 positive lines, expression is heterogeneous and the number of cells expressing high levels of the epitope is increased when the hybridomas are maintained at a relatively high cell density. Neuriminidase and pronase deplete the epitope recognized by mAb 984D4.6.5. Protein synthesis and glycosylation inhibitors also reduce expression of this epitope. These observations suggest that the epitope recognized by 984D4.6.5 is a carbohydrate linked to a polypeptide. This antibody was tested by ELISA for binding to a large panel of carbohydrates and glycolipids coupled to BSA. The only one that bound 984D4.6.5 was LS tetrasaccharide c (NeuNAc alpha 2-6Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc), an O-linked carbohydrate. Comparative analysis shows that both the sequence and the linkage of these sugars are essential to the reactivity with the 984D4.6.5 antibody. This epitope is expressed by a glycoprotein of approximately 200 kDa, as shown by Western blots. The identity of this glycoprotein remains to be determined, but indirect evidence suggests that it is not CD45.

Role of B70/B7-2 in CD4+ T-cell immune responses induced by dendritic cells.

Dendritic cells (DC) are potent antigen-presenting cells (APC). However, the molecular basis underlying this activity remains incompletely understood. To address this question, we generated murine monoclonal antibodies (mAb) against human peripheral blood-derived DC. One such antibody, designated IT209, stained differentiated DC and adherent monocytes, but failed to stain freshly isolated peripheral blood mononuclear cells (PBMC). The antigen recognized by IT209 was identified as B70 (B7-2; also recently identified as CD86). Using this mAb we studied the role of B70 in CD4+ T-cell activation by DC in vitro. IT209 partly inhibited the proliferative response of CD4+ T cells to allogeneic DC and to recall antigens, such as tetanus toxoid (TT) and purified protein derivative (PPD) of tuberculin, presented by autologous DC. More importantly, the mAb had a potent inhibitory effect on the primary response of CD4+ T cells to autologous DC pulsed with human immunodeficiency virus (HIV) gp160 or keyhole limpet haemocyanin (KLH). Adherent monocytes, despite their expression of B70, failed to induce T-cell responses to these antigens. IT209-mediated inhibition of CD4+ T-cell responses was equivalent to that produced by anti-CD25 mAb, whereas an anti-CD80 mAb was only marginally inhibitory and did not augment the effect of IT209. These findings indicate that the B70 antigen plays an important role in DC-dependent CD4+ T-cell activation, particularly in the induction of primary CD4+ T-cell responses to soluble antigens. However, since activated monocytes, despite their expression of B70, failed to prime naive T cells to these antigens, our results suggest that additional molecules contribute to the functions of DC in CD4+ T-cell activation.

Identification of a human OX-40 ligand, a costimulator of CD4+ T cells with homology to tumor necrosis factor.

The human OX-40 cell surface antigen is a CD4+ T cell activation marker that acts as a costimulatory receptor and is a member of the nerve growth factor receptor/tumor necrosis factor (TNF) receptor family. Using a soluble form of the receptor, the extracellular region fused with human immunoglobulin Fc, we expression cloned the human OX-40 ligand cDNA from a library derived from an activated B lymphoblastoid cell line MSAB. The encoded protein is identified as gp34, a type II transmembrane antigen previously known to be expressed only by human T cell lymphotropic virus 1-infected cells. We describe gp34 as a new member of the TNF family, and find that the recombinant ligand expressed in COS cells costimulates phorbol myristate acetate, phytohemagglutinin, and anti-CD3-induced CD4+ T cell proliferation.

Nonsteroidal anti-inflammatory drug therapy in chronic childhood iridocyclitis.

The adjunctive use of nonsteroidal anti-inflammatory drugs (NSAIDs) for the treatment of chronic iridocyclitis was evaluated in 14 patients, eight with juvenile rheumatoid arthritis and six with idiopathic iridocyclitis. In all patients, the activity of the iridocyclitis improved with the addition of NSAIDs to their treatment regimens, permitting reduction in the dose of corticosteroid drugs. These data suggest that NSAID therapy may have an adjunctive role in the treatment of chronic iridocyclitis in childhood.

Characterization of the choroidal mast cell.

The experimental studies performed on nonpigmented rat choroids and the review of the important literature covered in this thesis seem to justify the following statements: 1. Mast cells are present in the choroid in significant numbers. 2. Mast cell numbers vary considerably from one individual to another and from one location in the choroid to another. 3. The major concentration of mast cells in the uvea is in the posterior choroid. 4. The mast cells of the choroid have a preferential location along arterial vessels. 5. Choroidal mast cell population density apparently decreases with senescence. 6. Mast cell products are present in sufficient quantity to exert substantial effects on physiologic, immunologic, and inflammatory responses in the choroid. 7. Choroidal mast cell products are released with appropriate stimulation and share some properties with the connective-tissue mast cell. 8. Choroidal mast cell demonstrate enough differences to suggest that a local differentiation may be present and may represent a locally controlled modulating effect for choroidal physiologic, immunologic, and inflammatory reactions.

Arsonate-specific murine T cell clones. III. Correlation between clonotype expression and fine specificity for analogs of L-tyrosine-p-azobenzenearsonate.

Despite recent advances in our understanding of T cell antigen receptor structure, relatively little is known about the role of this receptor in MHC-restricted antigen recognition. To study this problem, we have developed a panel of ABA-Tyr-reactive, I-Ak-restricted T cell clones that differ in their ability to recognize structural analogs of ABA-Tyr. Three fine specificity groups have been defined. In each group, ABA-Tyr elicited the strongest response of any of the antigens tested. Group I clones responded to ABA-conjugated hydroxyphenyl-ethanol (ABA-HPE). Group II clones responded to ABA-conjugated hydroxyphenyl-methanol (ABA-HPM) but not to ABA-HPE, and group III clones responded only to ABA-Tyr. These studies show that differences as small as a single methylene group can dramatically affect fine specificity. Because these clones are all I-Ak-restricted, it was possible to correlate receptor serology with fine specificity. To this end, monoclonal anti-clonotypes were made against clone 16-F2 from group I and used to study the relationship between fine specificity and clonotype expression. A panel of 15 T cell clones studied with four anti-clonotype antibodies showed a strict correlation between clonotype expression and fine specificity. Taken together, these data suggest that the structure recognized by the anti-clonotype antibodies is a determinant of receptor fine specificity.