Breastfeeding following bariatric surgery among obese women with and without diabetes mellitus.

BACKGROUND: Information on exclusive breastfeeding (BF) and BF initiation following bariatric surgery (BS) among obese women with diabetes mellitus (DM) and without DM (non-DM) is limited. METHODS: Retrospective cohort study. Obesity was defined by BMI (kg/m2) as grade 1 (30-34.9), grade 2 (35-39.9) or grade 3 (≥40). The 65 women in the DM group (40 women with gestational, 19 with Type 2 and 6 with Type 1) was similar to 84 with non-DM in BS type: Roux-en-Y (51 vs 55%), sleeve gastrectomy (32 vs 35%), laparoscopic gastric banding (17 vs 7%) and gastro-duodenal anastomosis (0 vs 4%). RESULTS: Women with DM were older (35 vs 33y), of advanced age (54 vs 27%), with higher prevalence of grade 3 obesity (66 vs 46%), chronic hypertension (31 vs 10%), delivery of late-preterm infants (23 vs 10%) and neonatal hypoglycemia (25 vs 12%). Although infant feeding intention was similar: BF (66 vs 79%), partial BF (9 vs 7%) or formula (25 vs 14%), at discharge women with DM had lower exclusive BF (29 vs 41%) and BF initiation rates (68 vs 76%) than those with non-DM. Women with grade 3 obesity (52% were DM) differed from those with grades 1-2 (34% were DM) in exclusive BF (27 vs 52%), and BF initiation rates (66 vs 86%). CONCLUSION: After BS, women with DM, especially those with grade 3 obesity, had higher rates of chronic hypertension and preeclampsia and lower rates of exclusive BF and BF initiation than those who had DM but had less severe obesity.

Should We Hire Our Current Fellow? Hiring Trends and Preferences in Spine Surgery.

OBJECTIVE: To provide insight into hiring trends/preferences in Academic Orthopaedic Spine Surgery after fellowship training. METHODS: Fellowship directors (FDs) listed by the North American Spine Society were surveyed regarding new faculty hiring preferences. Surveys were analyzed/stratified by response using the Kruskal-Wallis with Dunn multiple comparisons test, the Fisher exact test, and the Mann-Whitney U test for univariate comparisons. RESULTS: Thirty-two of 52 (61.5%) FDs responded. 32.3% of graduated fellows pursued academic medicine, which was preferred by FDs (3.59 ± 0.67; 1 to 5 scale). From 2015 to 2020, of the 2.25 ± 1.46 faculty members hired per program, 45.8% were former residents/fellows. Top listed hiring qualities were "strong recommendation from a trusted colleague" (84.4%), "prior personal experience, as a resident/fellow" (78.1%), and "amicable personality" (53.1%). Twelve (38%) answered "no", six (19%) "yes", and 14 (44%) "other", regarding if hiring former residents/fellows benefits the field of spine surgery. "Other" answers endorsing in-house hiring most commonly mentioned consistency/stability (28.6%) while those opposed most commonly mentioned lack of diversity of training/novel techniques (42.9%). When considering programmatic size, while the stated perception of FDs regarding in-house hiring at larger (>2 fellows) versus smaller (1 to 2 fellows) programs was equivalent, the mean percentage of in-house hires at larger programs (67.8% ± 35.8%) was significantly greater than that of smaller programs (33.3% ± 44.8%, P = 0.04). CONCLUSIONS: In-house hiring in spine surgery appears to occur more commonly than perceived by program leadership, particularly at larger fellowship programs. Further study of hiring preferences and their impact on the field of spine surgery is warranted. STUDY DESIGN: Prospective Survey Study.

Ultrasound Measurements of the Median Nerve at the Distal Wrist Crease Correlate With Electrodiagnostic Studies.

Background: Carpal tunnel syndrome (CTS) is the most common nerve entrapment neuropathy and is commonly evaluated using electrodiagnostic studies (EDSs). Ultrasound (US) has emerged as a potentially easier and more comfortable alternative to EDSs. The purpose of this study is to evaluate whether measurements of the cross-sectional area (CSA) of the median nerve via US correlate with the severity rating of CTS based on EDSs. Methods: A retrospective review of patients aged 18 years or older who underwent US and EDSs of the median nerve for CTS was performed. Sensory nerve action potential, distal motor latency, and compound muscle action potential were measured, and severity was graded on American Association of Neuromuscular and Electrodiagnostic Medicine guidelines. Cross-sectional area of the median nerve was measured via US at the wrist crease. Results: There was a significant association between increasing CSA and increasing EDS severity (P < .0001). The mean CSA for normal, mild, moderate, and severe CTS was 7.48 ± 2.00, 10.36 ± 2.53, 12.01 ± 3.64, and 14.34 ± 4.77 mm2, respectively. The area under the curve demonstrated the ability of median nerve CSA to discriminate between normal and abnormal EDSs with an optimal cutoff CSA of ≥10 mm2, as well as, the ability to discriminate between mild CTS and moderate to severe CTS at a cutoff CSA of greater than or equal to 12 mm2. Conclusions: The results of this study show that US measurements of the median nerve at the distal wrist crease discriminate between normal and abnormal EDSs, and between mild CTS and moderate to severe CTS.

Corneal fibrosis abrogation by a localized AAV-mediated inhibitor of differentiation 3 (Id3) gene therapy in rabbit eyes in vivo.

Previously we found that inhibitor of differentiation 3 (Id3) gene, a transcriptional repressor, efficiently inhibits corneal keratocyte differentiation to myofibroblasts in vitro. This study evaluated the potential of adeno-associated virus 5 (AAV5)-mediated Id3 gene therapy to treat corneal scarring using an established rabbit in vivo disease model. Corneal scarring/fibrosis in rabbit eyes was induced by alkali trauma, and 24 h thereafter corneas were administered with either balanced salt solution AAV5-naked vector, or AAV5-Id3 vector (n = 6/group) via an optimized reported method. Therapeutic effects of AAV5-Id3 gene therapy on corneal pathology and ocular health were evaluated with clinical, histological, and molecular techniques. Localized AAV5-Id3 gene therapy significantly inhibited corneal fibrosis/haze clinically from 2.7 to 0.7 on the Fantes scale in live animals (AAV5-naked versus AAV5-Id3; p < 0.001). Furthermore, AAV5-Id3 treatment significantly reduced profibrotic gene mRNA levels: α-smooth muscle actin (α-SMA) (2.8-fold; p < 0.001), fibronectin (3.2-fold; p < 0.001), collagen I (0.8-fold; p < 0.001), and collagen III (1.4-fold; p < 0.001), as well as protein levels of α-SMA (23.8%; p < 0.001) and collagens (1.8-fold; p < 0.001). The anti-fibrotic activity of AAV5-Id3 is attributed to reduced myofibroblast formation by disrupting the binding of E-box proteins to the promoter of α-SMA, a transforming growth factor-ß signaling downstream target gene. In conclusion, these results indicate that localized AAV5-Id3 delivery in stroma caused no clinically relevant ocular symptoms or corneal cellular toxicity in the rabbit eyes.

Factors Impacting Recurrence Rate After Open Ganglion Cyst Excision.

Background: The recurrence rate after open excision of ganglion cysts is approximately 20%. However, this literature is based on a small series of subjects. This study aims to determine the rate and risk of recurrence after open excision of ganglion cysts in a large patient series. Methods: This study included 628 patients who had ganglion cyst excision from 2010 to 2018. A retrospective chart review recorded the following: age, sex, laterality, volar/dorsal location, and recurrence. An overall recurrence rate was calculated. In addition, a 1-way analysis of variance test was used to compare recurrence rates among the individual surgeons, and unpaired t tests were used to compare age of recurrence, dorsal cyst recurrence, laterality of cyst, and recurrence based on sex. Finally, a comparison of recurrence rate over time was conducted for surgeon 3. Results: The overall recurrence rate was 3.8% (24 of 628). The recurrence rates for each surgeon were 3% (9 of 353), 2% (3 of 167), and 11% (12 of 107), P = .02. The age of those with and without a recurrence did not differ (32 years vs 38 years), P = .06. The recurrence rate of dorsal ganglion cysts was 4.1% (14 of 341) compared with 3.5% (10 of 286) for volar ganglion cysts, P = .69. Male patients had a recurrence in 6.4% (13 of 204) of cases compared with 2.6% (11 of 424) of female patients, P = 0.01. There was a decrease in the rate of recurrence from 42.9% to 5.3% over 5 years for surgeon 3. Conclusion: In our sample, male sex and surgeon experience were significant risk factors in ganglion cyst recurrence.

Hsp90 inhibition protects the brain microvascular endothelium against oxidative stress.

The brain endothelium is an integral element of the blood-brain barrier (BBB). Dysfunction of this formation due to increased generation of reactive oxygen species (ROS) progresses the establishment of neurological disorders including stroke and traumatic brain injury. Heat shock protein 90 inhibitors are anti-inflammatory agents, and their activities are mediated, at least in part, by P53. This is a tumor suppressor protein which regulates the opposing activities of Rac1 and RhoA in the cellular cytoskeleton. In the present study we investigated the role of Hsp90 inhibitors in the H2O2-induced brain endothelium breakdown, by employing human cerebral microvascular endothelial cells (hCMEC/D3). Our findings suggest that H2O2 downregulates P53 by enhancing the P53 suppressor mouse double minute 2 homolog (MDM2), as well as by increasing the apyrimidinic endonuclease 1/redox factor 1 (APE1/Ref1). The H2O2 - triggered violation of the brain endothelium barrier was reflected in measurements of transendothelial resistance, and the increased expression of the key cytoskeletal modulators cofilin and myosin light chain 2 (MLC2). Treatment of the hCMEC/D3 cells with Hsp90 inhibitors counteracted those events, and reduced the generation of the hydrogen peroxide - induced reactive oxygen species. Hence, our study suggests that Hsp90 inhibition supports the BBB integrity, and may represent a promising therapeutic approach for disorders associated with brain endothelium breakdown; including COVID-19.

Analysis of current testing practices for biallelic MUTYH mutations in MUTYH-associated polyposis.

MUTYH-associated polyposis (MAP) is an autosomal recessive syndrome caused by biallelic mutations in the base excision repair gene MUTYH. Owing to potential limitations in the MAP testing strategy and testing criteria, it is possible that MAP is being under-identified both genotypically and phenotypically. To determine whether full sequencing of MUTYH would increase clinical sensitivity over a founder mutation (FM) strategy, a retrospective analysis of two datasets from a commercial clinical laboratory was performed. The first cohort contained 1522 individuals who received MUTYH analysis for two FMs with subsequent full-gene sequencing. Eighty-five biallelic individuals were identified; 47 carried two FMs, 17 carried one FM and one mutation identified on full sequencing, and 21 carried biallelic mutations identified only on full sequencing. The second cohort contained 921 patients with colorectal cancer <50 years and <10 reported colorectal adenomas who had undergone MUTYH mutation testing. In this cohort, 19 of 921 (2.1%) individuals were identified as biallelic MUTYH carriers. Of these, 13 did not have a personal or family history of polyps and would not have met guidelines for MUTYH testing. These results suggest that individuals with biallelic MUTYH mutations are under-ascertained based on both genotype and phenotype under current standard testing practices.

Breastfeeding initiation in women with gestational diabetes mellitus.

BACKGROUND: In the United States, breastfeeding initiation (BFI) is reported for 75% of all live births; however, little information is available regarding mothers affected by gestational diabetes mellitus (GDM). OBJECTIVE: To examine feeding practices and factors associated with BFI in women with GDM and their infants. METHODS: A total of 303 GDM (58 late preterm and 245 term) pregnancies were studied. Infant feeding preference was ascertained on admission to labor and delivery. Variables known to influence BFI including maternal age, smoking, obesity, racial and educational characteristics were assessed. RESULTS: On admission 188 women intended to BF, 60 intended to feed formula and 55 were undecided. None of the women who wished to feed formula and 27% of the originally undecided later initiated BF. Regardless of feeding preference 163 (54%) of all mothers initiated BF. Similar BFI rates were found for 176 Class A1 and 127 class A2 women. Logistic regression analysis showed that intention to BF was the most significant predictor of BFI. Factors associated with BFI failure included African American race, lower education, smoking, obesity and admission to NICU. Following delivery 264 (87%) infants received well baby care while 39 (13%) were admitted to the NICU. Among 188 women who intended to BF, BFI involved 81% of 160 infants receiving well baby care and 61% of the 28 admitted to the NICU. CONCLUSIONS: More than half of women with GDM, who intended to BF, initiated BF. BFI failure remains associated with race, lower education level, smoking, obesity, preference for formula feeding and admission to NICU.

Multiple large pilomatricomas in the setting of diffuse epidermal nevi.

Epidermal nevi are hamartomas arising from the embryonic ectoderm during early embryonic stages, resulting in cutaneous mosaicism. We describe a patient with diffuse epidermal nevi and multiple large pilomatricomas arising near or within epidermal nevi.

Epstein-Barr virus and multiple sclerosis: cellular immune response and cross-reactivity.

We investigated T cell immunity to Epstein-Barr virus (EBV) in multiple sclerosis (MS) and assessed cross-reactivity of the anti-EBV cellular response with brain antigens. We measured the proliferation, cytotoxicity, and number of interferon-γ secreting cells following stimulation with autologous EBV-infected lymphoblastoid cell lines (LCL) in MS patients and matched controls. There were no statistically significant differences for any of the measured responses, but there was a trend towards decreased proliferative responses in MS patients. There was no measured cross-reactivity between LCL and brain antigens. We conclude that the cellular immune response against EBV-infected cells is neither increased nor decreased in MS.

A planned randomized clinical trial of treatment for mild gestational diabetes mellitus.

OBJECTIVE: A planned study is described which will determine whether a benefit exists for the treatment of mild carbohydrate intolerance during pregnancy. METHODS: A randomized clinical trial of women with mild gestational diabetes will compare perinatal outcomes in those receiving diet therapy and insulin as required versus those randomized to no specific treatment. RESULTS: The primary outcome of this study will be a composite of neonatal morbidity in the treatment and control groups. CONCLUSIONS: A randomized treatment trial of mild gestational diabetes mellitus will clarify whether identification and treatment of mild gestational diabetes mellitus reduces perinatal morbidity. This information will aid in selecting appropriate thresholds for the treatment of gestational diabetes mellitus.

Selective isopeptide bond formation: coupling ubiquitin(67-76) with histone 2A(114-128) by use of the transfer active ester condensation technique.

A peptide, ubiquitin(67-76)-histone 2A(114-128) fragment (UBH2AF), was synthesized by selective formation of an isopeptide bond between the C-terminus of ubiquitin(67-76) and the epsilon-amino group of lysine-119 in histone 2A(114-128) which contained 4 lysine residues at positions 118, 119, 125 and 127, respectively. The transfer active ester condensation technique, together with the Tnm amine protecting group, were used successfully in the peptide segment coupling reaction. [structure: see text]

Lymphohaematopoietic malignancy around all industrial complexes that include major oil refineries in Great Britain.

OBJECTIVES: To examine the incidence of lymphohaematopoietic malignancy around industrial complexes that include major oil refineries in Great Britain after recent public and scientific concern of possible carcinogenic hazards of emissions from the petrochemical industry. METHODS: Small area study of the incidence of lymphohaematopoietic malignancies, 1974-91, within 7.5 km of all 11 oil refineries (grouped into seven sites) in Great Britain that were operational by the early 1970s and processed more than two million tonnes of crude oil in 1993. RESULTS: Combined analysis of data from all seven sites showed no significant (p < 0.05) increase in risk of these malignancies within 2 km or 7.5 km. Hodgkin's lymphoma, but no other malignancy, showed evidence (p = 0.02) of a decline in risk with distance from refineries, but there was an apparent deficit of cases of multiple myeloma near the refineries (p = 0.04). CONCLUSION: There was no evidence of association between residence near oil refineries and leukaemias, or non-Hodgkin's lymphoma. A weak positive association was found between risk of Hodgkin's disease and proximity to major petrochemical industry, and a negative association with multiple myeloma, which may be chance findings within the context of multiple statistical testing.

Cancer incidence and mortality around the Pan Britannica Industries pesticide factory, Waltham Abbey.

OBJECTIVES: To examine the incidence and mortality of cancer near the Pan Britannica Industries factory, Waltham Abbey, after reports of a possible cluster of all cancers and brain cancer in the vicinity. METHOD: Small area study of cancer incidence 1977-89, and mortality 1981-92, within a 7.5 km radius of the factory site. Postcoded cancer registrations and deaths in the study area were extracted from national data sets held by the Small Area Health Statistics Unit and compared with expected numbers computed by applying national rates stratified for age, sex, and deprivation to the local population (1981 and 1991 censuses). Observed/ expected (O/E) ratios were examined from 0-1 km and 0-7.5 km of the plant, and tests applied for a decline in relative risk with distance up to 7.5 km. RESULTS: There were 12,859 incidence cancers (1977-89) from 0-7.5 km (O/E ratio 1.04; 95% confidence interval (95% CI) 1.02 to 1.06) and 385 from 0-1 km (O/E 1.10; 1.00 to 1.22). There was an excess of skin melanoma from 0-1 km based on 11 cases (O/E 2.13; 1.06 to 3.80), and an excess from 0-7.5 km of cancer of the lung, stomach and pancreas combined, and prostate (O/Es ranged from 1.09 to 1.13). Only the findings from lung cancer were suggestive of a decline in risk with distance, especially in the later period (1982-9). There were 9196 cancer deaths (1981-92) from 0-7.5 km (O/E 1.04; 95% CI 1.02 to 1.06) and 308 from 0-1 km (O/E 1.24; 1.11 to 1.39); and 25507 non-cancer deaths (O/E 1.02; 1.01 to 1.04) from 0-7.5 km and 745 (O/E 1.14; 1.06 to 1.22) from 0-1 km. There was evidence of a decline in mortality with distance for all cancers combined, lung cancer (P = 0.001 for each), and colorectal cancer (P < 0.05), and also for non-cancers (P = 0.001). Proportional mortality analyses suggested a decline in risk with distance for lung cancer (P = 0.003) but not for all cancers or the site specific cancers examined. There was no evidence of an excess in the incidence or mortality from brain cancer. For cancer mortality in the inner-most wards, the findings were, for the most part, well within the range of variation across the region as a whole. CONCLUSIONS: The study provides limited and inconsistent evidence for a localised excess of cancer in the vicinity of the PBI plant. At present, further investigation does not seem warranted other than continued surveillance of mortality and cancer incidence in the locality.

Extraction and protein sequencing of immunoglobulin light chain from formalin-fixed cerebrovascular amyloid deposits.

Substantial amounts of a single protein have been extracted into electrophoresis sample buffer from archived formalin-fixed brain blood vessels, taken from a case of cerebral amyloidosis. Cyanogen bromide cleavage and tryptic digestion of the protein on Western blots allowed amino acid sequences from three resultant peptides to be determined. Comparison of these peptides with database sequences identified the extracted protein as being derived from an immunoglobulin light chain. This is the first demonstration of amino acid sequencing of a polypeptide extracted from formalin-fixed tissue. This case also appears to be unique, since primary cerebrovascular amyloidosis involving immunoglobulin light chains has not been previously described. The amyloid protein had clearly resisted formalin fixation; it is possible that this resistance occurred because the protein was deposited in large amounts as insoluble densely packed aggregates, which may exclude infiltration of the formalin. This technique may therefore have applications in the post-mortem diagnosis of amyloidoses and in the purification of other amyloids.

Pathological lesions of Alzheimer's disease and dementia with Lewy bodies brains exhibit immunoreactivity to an ATPase that is a regulatory subunit of the 26S proteasome.

MS73 is one of a family of ATPases that act as regulatory subunits of the 26S proteasome. Localisation of this ATPase in histological sections of hippocampus from Alzheimer's disease (AD) and in cingulate gyrus sections of dementia with Lewy bodies (DLB) brains was examined immunohistochemically. In all cases of AD (n = 10) neurofibrillary tangles (NFT), plaque neurites and neuropil threads were immunoreactive for MS73. In seven out of the nine cases of DLB, distinctive MS73-positive structures were detected within cortical Lewy bodies. The association of MS73 with these neuronal abnormalities provides further evidence that proteolytic processing involving the 26S proteasome occurs in lesions of AD and DLB.

Gestational diabetes survey.

OBJECTIVE: Our purpose was to determine how residents in obstetrics and gynecology and fellows in maternal-fetal medicine are currently being trained to diagnose and manage gestational diabetes mellitus. STUDY DESIGN: Questionnaires were mailed to 202 obstetrics and gynecology residency program directors and 78 maternal-fetal medicine fellowship directors. RESULTS: Sixty-four (82%) of the maternal-fetal medicine directors versus 142 (70%) of the residency directors responded. Universal screening, use of a 50 gm glucose challenge with a 1-hour-postingestion sample, no requirements for fasting before the screening test, use of two abnormal values on the 3-hour glucose tolerance test to define gestational diabetes mellitus, and initiation of insulin for elevated fasting glucose levels in spite of diet therapy were each recommended by > 90% of the respondents. CONCLUSION: Although the optimal management of gestational diabetes mellitus remains controversial, program directors are in general agreement with many aspects of the diagnosis and management.

The expression of alpha B-crystallin in epithelial tumours: a useful tumour marker?

Alpha B-crystallin is a lens protein showing homology with small heat-shock proteins. We have previously demonstrated its expression in non-lenticular normal and diseased human tissues by immunostaining with a polyclonal antibody. In view of the expression seen in normal renal tubular epithelium, we have assessed the immunoreactivity of a variety of epithelial tumours, to determine the usefulness of alpha B-crystallin as a specific renal tumour marker. Carcinomas arising from tissues which normally express alpha B-crystallin, such as colo-rectal and thyroid carcinomas, showed a varying pattern and degree of immunoreactivity. The most consistently positive tumours, however, with typically strong cytoplasmic and cell membrane staining, were renal cell carcinomas, 90 per cent of which showed positive immunoreactivity. This pattern of staining, while not absolutely specific, is a useful aid to the diagnosis of renal carcinoma. When a metastic deposit or a small biopsy is being assessed, anti-alpha B-crystallin may be included in a panel of antibodies, the pattern of staining of which may direct the search for the primary site of the tumour.

The differential effects of body fat distribution on insulin and glucose metabolism during pregnancy.

OBJECTIVE: Our purpose was to investigate whether maternal obesity, or more specifically body fat distribution, is associated with alterations in carbohydrate metabolism during pregnancy. STUDY DESIGN: A longitudinal study of oral glucose tolerance tests, insulin, C peptide, and glucagon levels during each trimester and post partum was undertaken in nine lean and 14 obese women. Obese women were divided into lower body obese (n = 6, waist/hip ratio < 0.9) and upper body obese (n = 8, waist/hip ratio > or = 0.9). RESULTS: Fasting blood glucose levels declined with advancing gestation only in lean subjects. Upper body obese women demonstrated maximal glucose response and insulin area under the curve by the second trimester, whereas lean and lower body obese women did not until the third trimester. Insulin areas were significantly elevated in upper body obese compared with lower body obese women (second trimester, p < 0.01; third trimester, p < 0.03; post partum p < 0.05). In contrast, C peptide levels were similar in obese subgroups and were significantly elevated only when compared with those of lean women. C peptide/insulin molar ratios were lower in upper body obese women during the second trimester (4.3 +/- 0.8) and third trimester (4.2 +/- 0.7) compared with lean (6.5 +/- 1.3, 6.7 +/- 0.5) and lower body obese women (7.9 +/- 1.4, 6.5 +/- 1.4) (p < 0.01). A significant relationship between waist/hip ratio and glucose level (r = 0.70, p < 0.004) and insulin areas (r = 0.76, p < 0.001) was present in late pregnancy in obese subjects. CONCLUSIONS: Relative hyperinsulinemia and earlier maximal glucose response in upper body obese women suggests that body fat distribution may explain the metabolic heterogeneity present in obese women during pregnancy. Body fat topography may serve as a potential marker for the early development of carbohydrate intolerance during pregnancy.