Single or double? A comparison of evisceration techniques.

PURPOSE: We compared the rates of implant exposure and extrusion after evisceration with single and double scleral closure techniques. METHODS: This retrospective cohort study included all patients who underwent evisceration with an implant insertion over the past 18 years at Tung Wah Eastern Hospital and Pamela Youde Nethersole Eastern Hospital. Clinical documents and operation records were reviewed. RESULTS: A total of 81 ethnic Chinese patients (44 male) who underwent evisceration with primary implant insertion were reviewed. 39 (48%) patients underwent the double scleral closure technique with an implant placed posterior to the posterior sclera, and 42 (52%) patients underwent the single scleral closure technique with an implant inserted in the intra-scleral cavity. The follow-up interval was 70 months. The surgical indications were endophthalmitis (35%), painful blind eye (23%), traumatic disfigured globe (22%) and phthisis bulbi (20%). Silicone was the most used implant material (69%). The patients who underwent double scleral closure had a larger size of the implant (19.7 vs 17.9 mm, p < 0.05). Both implant exposure (26% vs 3%, p < 0.05) and implant extrusion (26% vs 0%, p < 0.05) were more common in patients who underwent single scleral. CONCLUSIONS: Double scleral closure technique allows a larger implant, and it is associated with a lower rate of implant exposure and extrusion. The double scleral closure technique is a superior technique of choice in these patients with primary implant placement.

A Review of Tolerance and Safety Profiles of Long-Term Botulinum Neurotoxin Type A in Asian Patients with Hemifacial Spasm and Benign Essential Blepharospasm.

This article reports the tolerance and long-term safety profiles of botulinum neurotoxin type A among Asian patients with benign essential blepharospasm (BEB) and hemifacial spasm (HFS). We performed a retrospective review of clinical documents and procedure records of consecutive BEB and HFS patients receiving onabotulinum toxin A (Botox) treatment in our clinic over the past 20 years. We reviewed the information of 105 patients diagnosed with BEB (n = 31) and HFS (n = 74). All of the patients were Asian. The mean age of disease onset was 59 (range 37-80) years old for BEB and 61 (range 31-83) for HFS. The mean follow up was 84 (range 12-240) months and the mean number of sessions per patient was 19 (range 1-61). The botulinum toxin dose per session increased significantly in both BEB (16.5 versus 21.6 units, p < .05) and HFS (22.6 versus 26.9 units, p < .05) patients after a mean of 18 sessions; however, the onset time, effective duration and subjective treatment outcome were similar over time in both BEB and HFS patients. At least one local complication was reported among 26% and 41% of patients with BEB and HFS respectively, with ptosis (32%) being most frequent.

Choroidal thickness in thyroid-associated orbitopathy.

IMPORTANCE: To investigate the choroidal thickness (CT) in patients with thyroid-associated orbitopathy (TAO). BACKGROUND: To compare CT of TAO patients and healthy subjects. DESIGN: Prospective cross-sectional study in a public hospital. PARTICIPANTS: One hundred and four eyes of 52 TAO patients and 52 eyes of 26 healthy subjects. METHODS: CT was measured with enhanced-depth imaging optical coherence tomography (EDI-OCT) at the subfoveal, macular and peripapillary regions. Multivariate linear regression was used to evaluate the associations of subfoveal CT with systemic and ocular variables among TAO eyes. MAIN OUTCOME MEASURES: CT of both groups. RESULTS: CT of eyes with TAO was significantly increased at the subfoveal region, 1 and 2 mm from the fovea nasally, temporally and superiorly, and 1 mm inferior to the fovea (all P < .05). No significant difference was found in CT at 2 mm inferior to the fovea (P = .094) and all four quadrants of the peripapillary region (superior, P = .096; nasal, P = .732; inferior, P = .179; temporal, P = .052). Among TAO eyes, thinner subfoveal choroid was associated with worsening exophthalmos (P = .043), poorer visual acuity (P = .017), increasing age (P = .040) and axial length (P < .001). There was no association between CT and clinical activity score (P = .239). CONCLUSIONS AND RELEVANCE: TAO patients showed thicker choroid than controls over the macula, but not the peripapillary regions. Thinner subfoveal choroid was associated with worsening exophthalmos and poorer vision. EDI-OCT can monitor choroidal vascular changes associated with TAO and its complications.

Compartment-specific immunity in the human gut: properties and functions of dendritic cells in the colon versus the ileum.

OBJECTIVE: Dendritic cells (DC) mediate intestinal immune tolerance. Despite striking differences between the colon and the ileum both in function and bacterial load, few studies distinguish between properties of immune cells in these compartments. Furthermore, information of gut DC in humans is scarce. We aimed to characterise human colonic versus ileal DC. DESIGN: Human DC from paired colonic and ileal samples were characterised by flow cytometry, electron microscopy or used to stimulate T cell responses in a mixed leucocyte reaction. RESULTS: A lower proportion of colonic DC produced pro-inflammatory cytokines (tumour necrosis factor-α and interleukin (IL)-1ß) compared with their ileal counterparts and exhibited an enhanced ability to generate CD4(+)FoxP3(+)IL-10(+) (regulatory) T cells. There were enhanced proportions of CD103(+)Sirpα(-) DC in the colon, with increased proportions of CD103(+)Sirpα(+) DC in the ileum. A greater proportion of colonic DC subsets analysed expressed the lymph-node-homing marker CCR7, alongside enhanced endocytic capacity, which was most striking in CD103(+)Sirpα(+) DC. Expression of the inhibitory receptor ILT3 was enhanced on colonic DC. Interestingly, endocytic capacity was associated with CD103(+) DC, in particular CD103(+)Sirpα(+) DC. However, expression of ILT3 was associated with CD103(-) DC. Colonic and ileal DC differentially expressed skin-homing marker CCR4 and small-bowel-homing marker CCR9, respectively, and this corresponded to their ability to imprint these homing markers on T cells. CONCLUSIONS: The regulatory properties of colonic DC may represent an evolutionary adaptation to the greater bacterial load in the colon. The colon and the ileum should be regarded as separate entities, each comprising DC with distinct roles in mucosal immunity and imprinting.

IL-6 promotes immune responses in human ulcerative colitis and induces a skin-homing phenotype in the dendritic cells and Tcells they stimulate.

Dendritic cells (DCs) control the type and location of immune responses. Ulcerative colitis (UC) is considered a Th2 disease mediated by IL-13 where up to one third of patients can develop extraintestinal manifestations. Colonic biopsies from inflamed and noninflamed areas of UC patients were cultured in vitro and their supernatants were used to condition human blood enriched DCs from healthy controls. Levels of IL-13 in the culture supernatants were below the detection limit in most cases and the cytokine profile suggested a mixed profile rather than a Th2 cytokine profile. IL-6 was the predominant cytokine found in inflamed areas from UC patients and its concentration correlated with the Mayo endoscopic score for severity of disease. DCs conditioned with noninflamed culture supernatants acquired a regulatory phenotype with decreased stimulatory capacity. However, DCs conditioned with inflamed culture supernatants acquired a proinflammatory phenotype with increased expression of the skin-homing chemokine CCR8. These DCs did not have decreased T-cell stimulatory capacity and primed T cells with the skin-homing CLA molecule in an IL-6-dependent mechanism. Our results highlight the role of IL-6 in UC and question the concept of UC as a Th2 disease and the relevance of IL-13 in its etiology.

Surgical outcomes of orbital evisceration with primary orbital implant placement in patients with endophthalmitis.

OBJECTIVES: This study reports the surgical outcomes of evisceration with primary orbital implant placement in patients with endophthalmitis and analyses the association with implant exposure and extrusion. METHODS: A retrospective, multicentre, Chinese cohort study. Review of medical records and orbital images of patients who underwent evisceration with primary orbital implant placement between January 2005 and January 2021. RESULTS: Out of 79 patients who underwent orbital evisceration with primary orbital implant placement, 26 (26 eyes) of them (male = 13) suffered from endophthalmitis. The duration from endophthalmitis diagnosis (19 = exogenous, 7 = endogenous) to evisceration was 9 standard deviation ± 5 (range: 1-15) days. The follow-up was 70 ± 46 (24-180) months after operation. The orbital implant size was 17 ± 3 (14-20) mm, and silicone was the most used material (69%, 18/26 of patients). The most frequent post-operative complication was orbital implant exposure (42%, 11/26), followed by orbital implant extrusion (12% 3/26) and ptosis (8%, 2/26). Implant exposure or extrusion was more commonly associated with endophthalmitis in comparison to non-endophthalmitis patients that required evisceration and primary orbital implant placement (54% versus 17%, P < 0.05). Univariate analysis showed single scleral closure technique (100% versus 58%, P < 0.05) and endogenous endophthalmitis (50% versus 0%, P < 0.05) were associated with implant exposure or extrusion, and only endogenous endophthalmitis was significant with multivariate analysis (P < 0.05). CONCLUSIONS: Primary implant placement during evisceration should be avoided in eyes with endophthalmitis especially in those with an endogenous source, and double scleral closure technique may be a better alternative for primary orbital implant placement in infected eyes.

Ocular Surface Evaluation in Immunoglobulin G4-Related Ophthalmic Disease.

PURPOSE: To evaluate the functional and structural changes of the meibomian glands and ocular surface in immunoglobulin G4-related ophthalmic disease (IgG4-ROD) patients. DESIGN: Cross-sectional, matched case-control comparison study. METHODS: This study included 64 patients with biopsy-proven IgG4-ROD (aged 63.4 ± 12.2 years, 39 male) and 64 sex- and age-matched healthy controls. Patients were managed by hospitals covering the publicly funded ophthalmology service in Hong Kong. Outcome measures included anterior segment examination and keratographic and meibographic imagings. RESULTS: A total of 64 worst-affected eyes of the 64 IgG4-ROD patients were analyzed. Corneal fluorescein staining (P = .0187), lid margin telangiectasia (P = .0360), lid-parallel conjunctival folds (P = .0112), papillae (P = .0393), meibomian gland plugging (P = .0001), meibomian gland expressibility (P = .0001), and meibum quality (P = .0001) were more significant in IgG4-ROD patients compared with healthy controls. Both upper and lower meibomian gland dropouts (P = .001 and .0003), and tear meniscus height (P = .0001) were higher in IgG4-ROD patients. Non-invasive tear break-up time (NITBUT) (P = .0166) and Schirmer test results (P = .0243) were lower in IgG4-ROD patients. Upper (r = 0.336, P = .0140) meibomian gland dropouts and NITBUT (r = -0.293, P = .0497) were positively and negatively correlated with the IgG4-ROD onset age, respectively. The number of extraocular organ involvement was negatively correlated with the Schirmer test(r = -0.341, P = .0167). Lower NITBUT was found in IgG4-ROD eyes with lacrimal gland enlargement than in IgG4-ROD eyes without lacrimal gland enlargement radiologically (P < .0001). CONCLUSIONS: IgG4-ROD patients showed features of both aqueous tear deficiency and evaporative dry eye disease. We recommend ocular surface evaluation to all patients newly diagnosed with IgG4-ROD. Further studies are warranted to clarify the mechanism of IgG4-related dry eye disease.

Treatment outcomes and their determinants of IgG4-related ophthalmic disease: a territory-wide cohort study.

BACKGROUND: Oral corticosteroid remains the first-line treatment of IgG4-related ophthalmic disease, but steroid-dependence is common and serious. Factors associated with steroid dependence and relapse have to be further explored. STUDY POPULATION: A city-wide, biopsy-proven, Chinese cohort. METHODS: Retrospective, masked review of medical records, orbital images and histopathology reports. RESULTS: There were 101 patients with at least 24-month follow-up. Up to 82% (82/101) received oral corticosteroid as first-line treatments, and 7 of them received also concomitant steroid-sparing agents (SSA)/biological agents as primary treatment. There was 61% (50/82) of patients required long-term corticosteroid (alone=23, with SSA=27) after 1.9±0.7 (range 1-5) relapses. When compared with the 21% (17/82) of patients who tapered corticosteroid successfully for 24 months, steroid dependence was associated with elevated baseline serum IgG4 level (94% vs 65%, p<0.01) and Mikulicz syndrome (46% vs 18%, p<0.05). Up to 13% (11/82) of patients tolerated residual disease after tapering off corticosteroid. There was 17% (17/101) of patients did not require any medications after biopsies. They were more likely to have debulking surgeries (71% vs 40%, p<0.05), discrete orbital lesions (65% vs 26%, p<0.05), normal baseline serum IgG4 level (24% vs 6%, p<0.05) and no Mikulicz syndrome (94% vs 61%, p<0.05). CONCLUSION: In this cohort, 60% of patients required long-term maintenance oral corticosteroid. Elevated pretreatment serum IgG4 level and Mikulicz syndrome were associated with steroid dependence. Debulking surgery is an alternative for a subgroup of patients with discrete orbital lesions, normal baseline IgG4 level and no Mikulicz syndrome.

Malignancies in Immunoglobulin G4-related ophthalmic disease.

PURPOSE: Clinical phenotypes in Immunoglobulin G4-related disease (IgG4-RD) according to the patterns of affecting organs have different risks of malignancies. We attempt to determine the association of malignancies with IgG4-related ophthalmic disease (IgG4-ROD). DESIGN: Retrospective cohort study. METHODS: Review of medical records, orbital images and histopathology reports in a territory-wide cohort of biopsy proven IgG4-ROD patients from 2005-2019. FINDINGS: Among 122 patients who had biopsies taken from adnexal lesions including lacrimal glands (n = 108), orbital mass (n = 30), infiltrated orbital fat (n = 10), conjunctiva (n = 2) or extraocular muscles (n = 3), 13% (16/122) developed malignancies over 73 ± 48months' follow-up. There were 9 cases of ocular adnexal lymphoma (OAL) and 7 extra-orbital malignancies. Compared with the general population, the incidence of OAL was significantly higher (standardized incidence ratios, SIRs = 10.0, 95%CI = 4.5-17.6) while that of extra-orbital malignancies was similar. The SIRs was highest within the first year (SIR = 46.7, 95%CI = 18.5-87.6) when 7 OAL were concomitantly diagnosed. Patients who developed OAL or extra-orbital malignancies were older than other patients at IgG4-ROD diagnosis (64.9 ± 7.1, 68.3 ± 8.5 versus 55.2 ± 15.0 years, P < 0.05). Asymmetric lacrimal gland enlargement (78% versus 13%), lack of frontal (0% versus 12%) or infraorbital nerve enlargement (0% versus 36%) were associated with OAL (all P < 0.05). Pre-treatment serum IgG4 level or extra-orbital IgG4-RD involvement was similar among patients with or without malignancies. CONCLUSION: In this biopsy-proven IgG4-ROD cohort, 7% developed OAL which was 10 times higher than the general population. Patients with asymmetric lacrimal gland enlargement or without trigeminal nerves involvement radiologically were associated with OAL.

A dangerous combination of binge and purge.

We present a 36-year-old female diagnosed with Crohn's disease at the age of 11 years. In 2001, she underwent a total colectomy and further small bowel resection as a result of active Crohn's. Her residual anatomy consisted of 150 cm of small bowel to an end jejunostomy. Subsequently, she developed short bowel syndrome with recurrent episodes of hypomagnesaemia, hypocalcaemia, and hypokalaemia. Dietetic assessment revealed her to be severely underweight at 37 kg with a bodymass index (BMI) of 14.4 kg/m(2) . During her admission, our patient underwent psychiatric assessment and was established on home parenteral nutrition (HPN). At the time of discharge, 1 month later, her weight had increased to 44 kg (BMI = 17.7 kg/m(2) ). Over the following 12-month period, she lost weight (BMI, 15.4 mg/m(2) ; weight, 39.5 kg) and she described a high stoma output (up to 17 L) and dehydration. Assessment of her oral intake found she was consuming an estimated 14,000 kcal and 600 g protein per day. At this time, the possibility of a new form of eating disorder was discussed with the patient and she agreed that her behavior i.e., using her stoma as a purging device, fulfilled the criteria for a diagnosis of bulimia nervosa and she was referred to a specialist eating disorder unit.

H1N1 vaccines in a large observational cohort of patients with inflammatory bowel disease treated with immunomodulators and biological therapy.

BACKGROUND: Safety data are lacking on influenza vaccination in general and on A (H1N1)v vaccination in particular in patients with inflammatory bowel disease (IBD) receiving immmunomodulators and/or biological therapy. AIMS AND METHODS: The authors conducted a multicentre observational cohort study to evaluate symptoms associated with influenza H1N1 adjuvanted (Pandemrix, Focetria, FluvalP) and non-adjuvanted (Celvapan) vaccines and to assess the risk of flare of IBD after vaccination. Patients with stable IBD treated with immunomodulators and/or biological therapy were recruited from November 2009 until March 2010 in 12 European countries. Harvey-Bradshaw Index and Partial Mayo Score were used to assess disease activity before and 4 weeks after vaccination in Crohn's disease (CD) and ulcerative colitis (UC). Vaccination-related events up to 7 days after vaccination were recorded. RESULTS: Of 575 patients enrolled (407 CD, 159 UC and nine indeterminate colitis; 53.9% female; mean age 40.3 years, SD 13.9), local and systemic symptoms were reported by 34.6% and 15.5% of patients, respectively. The most common local and systemic reactions were pain in 32.8% and fatigue in 6.1% of subjects. Local symptoms were more common with adjuvanted (39.3%) than non-adjuvanted (3.9%) vaccines (p < 0.0001), whereas rates of systemic symptoms were similar with both types (15.0% vs 18.4%, p = 0.44). Among the adjuvanted group, Pandemrix more often induced local reactions than FluvalP and Focetria (51.2% vs 27.6% and 15.4%, p < 0.0001). Solicited adverse events were not associated with any patient characteristics, specific immunomodulatory treatment, or biological therapy. Four weeks after vaccination, absence of flare was observed in 377 patients with CD (96.7%) and 151 with UC (95.6%). CONCLUSION: Influenza A (H1N1)v vaccines are well tolerated in patients with IBD. Non-adjuvanted vaccines are associated with fewer local reactions. The risk of IBD flare is probably not increased after H1N1 vaccination.

Radiological Determinants of Complicated Immunoglobulin G4-Related Ophthalmic Disease: A Territory-Wide Cohort Study.

PURPOSE: To evaluate the presenting radiological features of immunoglobulin G4-related ophthalmic disease (IgG4-ROD) and their associations with IgG4-related optic neuropathy (IgG4-RON), and IgG4-related ocular adnexal lymphoma (IgG4-ROL). METHODS: A territory-wide, biopsy-proven, Chinese cohort. Masked review of orbital images, medical records, and histopathology reports. RESULTS: A total of 115 (94%) of the 122 patients in our cohort had preoperative orbital images (computed tomography=105, magnetic resonance imaging=40). Among them, 103/115 (90%) showed enlarged lacrimal glands, and 91 (88%) were bilateral. Nerve enlargement was observed: infraorbital in 31/115 (27%) patients and frontal in 17/115 (15%), 10 and 9 being bilateral, respectively. At least 1 or more extraocular muscle (EOM) enlargement was found in 41/115 (37%) patients, bilaterally in 20. Lateral rectus occurred in 30 (73%) of these 41 EOM patients and inferior rectus in 28 (68%). Two adjacent EOMs (inferior and lateral recti in 11 patients, inferior and medial recti in 7 patients) or multiple EOMs (at least 3) were enlarged in 23/41 (56%) and 13/41 (32%) of the patients, respectively. Intraconal lesions (67% vs 11%, P<0.05), infraorbital (83% vs 23%, P<0.005), or frontal (50% vs 15%, P<0.05) nerve enlargement was significantly associated with IgG4-RON (6 patients) by univariate analyses. Asymmetric lacrimal gland enlargement and discrete orbital mass (both P<0.05) were associated with IgG4-ROL (9 patients) by multivariate analyses. CONCLUSIONS: In this IgG4-ROD cohort, most patients had bilateral enlarged lacrimal glands, and the lateral rectus is the most frequently involved EOM. For the first time, unique radiological patterns associated with the development of IgG4-RON and IgG4-ROL are found.

Exotropic drift and ocular alignment after surgical correction for intermittent exotropia.

PURPOSE: To evaluate changes in the angle of deviation over time and compare the motor success rate with different initial postoperative deviation in patients undergoing surgical correction for intermittent exotropia. METHODS: Forty-eight patients aged between 1 and 10 years who underwent bilateral lateral rectus recession for intermittent exotropia were retrospectively evaluated. Preoperative and postoperative ocular deviations at 1 week, 1 month, and 6 months were analyzed. Full surgical correction was attempted in all patients. Motor success was defined as ocular deviation within 10 prism diopters of orthophoria at 6 months postoperatively. RESULTS: The follow-up period ranged from 6 months to 3 years. Although most patients had exotropic drift, this drift was greater in patients with initial esotropia (86.7%) and orthophoria (70.0%) compared to patients with exotropia (26.1%). Motor success was achieved in 29 (60.4%) patients. There was no statistical difference between ocular alignment at 1 week postoperatively and final motor success (P = .782). There was good correlation between ocular alignment at 1 week and 6 months postoperatively (rho = 0.585, P < .001). Age and preoperative deviation were not found to be associated with motor success. CONCLUSIONS: The success rate appears to be unaffected by initial ocular alignment, suggesting that deliberate initial overcorrection may be unnecessary. Future studies are warranted to evaluate the long-term stability of this alignment.

Use of transgenic mice to map cis-acting elements in the intestinal fatty acid binding protein gene (Fabpi) that control its cell lineage-specific and regional patterns of expression along the duodenal-colonic and crypt-villus axes of the gut epithelium.

The mouse intestinal epithelium is able to establish and maintain complex lineage-specific, spatial, and temporal patterns of gene expression despite its rapid and continuous renewal. A multipotent stem cell located near the base of each intestinal crypt gives rise to progeny which undergo amplification and allocation to either enterocytic, Paneth cell, goblet cell, or enteroendocrine cell lineages. Differentiation of these four lineages occurs during their geographically ordered migration along the crypt-villus axis. Gut stem cells appear to have a "positional address" which is manifested by differences in the differentiation programs of their lineal descendants along the duodenal-colonic (cephalocaudal) axis. We have used the intestinal fatty acid binding protein gene (Fabpi) as a model to identify cis-acting elements which regulate cell- and region-specific patterns of gene expression in the gut. Nucleotides -1178 to +28 of rat Fabpi direct a pattern of expression of a reporter (human growth hormone [hGH]) which mimics that of mouse Fabpi (a) steady-state levels of hGH mRNA are highest in the distal jejunum of adult transgenic mice and fall progressively toward both the duodenum and the mid-colon; and (b) hGH is confined to the enterocytic lineage and first appears as postmitotic, differentiating cells exit the crypt and migrate to the base of small intestinal villi or their colonic homologs, the surface epithelial cuffs. Nucleotides -103 to +28, which are highly conserved in rat, mouse and human Fabpi, are able to correctly initiate transgene expression in late fetal life, restrict hGH to the enterocytic lineage, and establish an appropriate cephalocaudal gradient of reporter expression. This cephalocaudal gradient is also influenced by cis-acting elements located between nucleotides -1178 and -278, and -277 and -185 that enhance and suppress (respectively) expression in the ileum and colon and by element(s) located upstream of nucleotide -277 that are needed to sustain high levels of hGH production after weaning. Nucleotides -277 to -185 contain part of a domain conserved between the three orthologous Fabpi genes (nucleotides -240 to -159), a 24-bp element (nucleotides -212 to -188) that binds nuclear factors present in colonic but not small intestinal epithelial cells, and a portion of a CCAAT/enhancer binding protein footprint (C/EBP alpha, nucleotides -188 to -167). Removal of nucleotides -277 to -185 (yielding I-FABP-184 to +28/hGH+3) results in inappropriate expression of hGH in proliferating and nonproliferating epithelial cells located in the mid and upper portions of duodenal, jejunal, ileal, and colonic crypts without affecting the "shape" of the cephalocaudal gradient of transgene expression.(ABSTRACT TRUNCATED AT 400 WORDS)

Sex-specific quantitative trait loci linked to autoresuscitation failure in SWR/J mice.

Autoresuscitation (AR) is a highly conserved response among mammals, which allows survival from transient extreme hypoxia. During hypoxia, bradycardia, and hypoxic gasping develop after a brief period of hyperactivity. Normally, AR occurs if oxygen is restored during the gasping period where an initial heart rate increase is rapidly followed resumption or eupneic breathing. Humans and other mammals can survive multiple immediately repeated AR. A defective AR capacity has been implicated in Sudden Infant Death Syndrome. We had reported earlier that inbred strains of mice such as BALB/cJ could survive a characteristic number of immediately repeated AR trials, but that SWR/J mice failed to AR from a single hypoxic episode. We now report that strains closely related to SWR/J, FVB/N and SJL/J exhibit partial resuscitation defects relative to BALB/cJ or other mouse strains, establishing a genetic basis for variation in AR failure. The AR trial phenotype of BALB/cJ x SWR/J intercross F(1) and F(2) mice was consistent with BALB/cJ dominance and a discrete number of loci. Genome-wide mapping conducted with 60 intercross F(2) animals linked two loci to the number of AR trials survived, including one sex-specific locus with male expression, consistent with the observed 50% male bias for Sudden Infant Death Syndrome in humans. A locus carried on SWR/J chromosome 10 seems to be particularly important in AR failure and was confirmed in a partial consomic line. These results establish a genetic basis for AR failure phenotype in mice, with relevance to Sudden Infant Death Syndrome.

Intestinal epithelial cell differentiation: new insights from mice, flies and nematodes.

Decisions commonly made during development that affect proliferation, cell fate specification, differentiation, migration, and death are made repeatedly in the mouse small intestinal epithelium throughout adulthood. The results of these decisions are a stratification of proliferation, differentiation, and death along the mouse small intestine's crypt/villus axis. Recent genetic studies in Caenorhabditis elegans and Drosophila melanogaster have identified factors involved in determining cell fate and differentiation in gut endoderm. The stem cell hierarchy of the adult mouse intestinal epithelium makes it ideally suited for using chimeric animals to examine the functions of homologs of these lower eukaryotic (and other) proteins.

Association of antenatal steroid and risk of retinopathy of prematurity: a systematic review and meta-analysis.

BACKGROUND: Retinopathy of prematurity (ROP) is one of the leading causes of childhood blindness. Use of antenatal steroid can reduce neonatal morbidity and mortality in preterm births, but its effect on ROP remained controversial. We aim to determine the association between antenatal steroid and risk of ROP by a systematic review and meta-analysis. METHODS: Reported studies on the association between antenatal steroid and risk of ROP or severe ROP were identified from MEDLINE and Embase databases from their inception to November 2016. Outcome measures were ORs with 95% CIs. Extracted data were pooled using a random-effect model or fixed-effect model where appropriate. Heterogeneity was assessed, and sensitivity analysis was performed. RESULTS: A total of 434 relevant studies were identified, and 28 studies were eligible for the meta-analysis, involving 20 731 neonates with 4202 cases of ROP. Among the 28 studies included, 13 studies provided data evaluating the association between antenatal steroid use and severe ROP, involving 4999 neonates with 792 cases of severe ROP. Antenatal steroid administration was associated with a reduced risk of ROP development (ORunadjusted=0.82, 95% CI 0.68 to 0.98; ORadjusted=0.67, 95% CI 0.47 to 0.94) and progression to severe ROP (ORunadjusted=0.58, 95% CI 0.40 to 0.86). CONCLUSION: Antenatal steroid administration is associated with a reduced risk of ROP development and progression to severe ROP. Our results strengthened the indications of antenatal steroid therapy to high-risk mothers giving preterm births, especially in low-income and middle-income countries where antenatal steroid are not yet widely used.

The Natural Course of Intermittent Exotropia over a 3-year Period and the Factors Predicting the Control Deterioration.

The natural course of intermittent exotropia and the factors affecting its control has been unclear. We aim to report the natural course of our cohort of 117 Chinese children with intermittent exotropia and to identify baseline parameters that may have predictive value in the control deterioration of the disease. The visual acuity, spherical equivalent, compliance to orthoptic exercise, angle of deviation fusional convergence parameters and Newcastle Control Score were recorded for all children at baseline and at 3 years apart. Patients were divided into two groups according to the change in control over the 3 years: group 1 included patients who had no deterioration or had improvement in disease control; and group 2 were those who had deteriorated control or had undergone surgery. There were 77 patients (66%) in group 1 and 40 (34%) patients in group 2. Comparing the baseline parameters of the two groups, group 1 had statistically significantly smaller angle of deviation, larger fusional reserve, larger fusional recovery, and higher fusional reserve ratio (p < 0.05). Other baseline parameters were similar between the two groups. The baseline fusional parameters may have predictive value in determining the control of intermittent exotropia.

Refractive Errors and Concomitant Strabismus: A Systematic Review and Meta-analysis.

This systematic review and meta-analysis is to evaluate the risk of development of concomitant strabismus due to refractive errors. Eligible studies published from 1946 to April 1, 2016 were identified from MEDLINE and EMBASE that evaluated any kinds of refractive errors (myopia, hyperopia, astigmatism and anisometropia) as an independent factor for concomitant exotropia and concomitant esotropia. Totally 5065 published records were retrieved for screening, 157 of them eligible for detailed evaluation. Finally 7 population-based studies involving 23,541 study subjects met our criteria for meta-analysis. The combined OR showed that myopia was a risk factor for exotropia (OR: 5.23, P = 0.0001). We found hyperopia had a dose-related effect for esotropia (OR for a spherical equivalent [SE] of 2-3 diopters [D]: 10.16, P = 0.01; OR for an SE of 3-4D: 17.83, P < 0.0001; OR for an SE of 4-5D: 41.01, P < 0.0001; OR for an SE of ≥5D: 162.68, P < 0.0001). Sensitivity analysis indicated our results were robust. Results of this study confirmed myopia as a risk for concomitant exotropia and identified a dose-related effect for hyperopia as a risk of concomitant esotropia.