Postnatal functional integrity of the brainstem auditory pathway in late preterm infants born of small-for-gestation age: how different from those born of appropriate-for-gestation.

It is unclear whether there is any postnatal abnormality in brainstem auditory function in late preterm small-for-gestational-age (SGA) infants. We investigated the functional integrity of the brainstem auditory pathway at 4 months after term in late preterm SGA infants and defined differences from appropriate-for-gestational age (AGA) infants. The maximum length sequence brainstem evoked response (MLS BAER) was recorded and analyzed in 24 SGA (birthweight < 3rd centile) infants and 28 AGA infants (birthweight > 10th centile). All infants were born at 33-36-week gestation without major perinatal and postnatal problems. We found that I-V interval in SGA infants was shorter than in AGA infants at higher click rates and significantly shorter at the highest rate of 910/s. Of the two smaller intervals, I-III interval was significantly shorter in SGA infants than in AGA infants at higher click rates of 455 and 910/s clicks, whereas III-V interval was similar in the two groups. The III-V/I-III interval ratio in SGA infants tended to be greater than in AGA infants at all rates and was significantly greater at 455 and 910/s clicks. The slope of I-III interval-rate functions in SGA infants was moderately smaller than in AGA infants.  Conclusions: The main and fundamental difference between late preterm SGA and AGA infants was a significant shortening in the MLS BAER I-III interval in SGA infants at higher click rates, suggesting moderately faster neural conduction in the caudal brainstem regions. Postnatal neural maturation in the caudal brainstem regions is moderately accelerated in late preterm SGA infants. What is Known: • At 40 weeks of postconceptional age, late preterm SGA infants manifested a mild delay in neural conduction in the auditory brainstem. What is New: • At 56 weeks of postconceptional age, late preterm SGA infants manifested moderately faster neural conduction in the caudal brainstem regions. • Postnatal neural maturation is moderately accelerated in the caudal brainstem regions of late preterm SGA infants.

How I Do It: Holmium laser cystolitholapaxy and enucleation of the prostate for benign prostatic hyperplasia.

Holmium enucleation of the prostate (HoLEP) is a gold-standard, size-independent surgical treatment for benign prostatic hyperplasia (BPH) distinguished for its efficacy in tissue removal, shorter catheterization durations, lower transfusion rates, and decreased hospital stays when compared to transurethral resection of the prostate (TURP). The objective of this article is to demonstrate the step-by-step procedure of holmium laser cystolitholapaxy and enucleation of the prostate for BPH, emphasizing a top-down modified two-lobe technique with early apical release which enhances visualization and irrigation flow during the enucleation process.

Postnatal abnormality in brainstem neural conduction in neonatal bronchopulmonary dysplasia survivors.

OBJECTIVE: To investigate postnatal neural conduction in the auditory brainstem in neonatal bronchopulmonary dysplasia (BPD) survivors. METHODS: Thirty-two very preterm BPD survivors were studied at 57-58 weeks of postconceptional age. Brainstem auditory-evoked response was studied using maximum length sequence. Wave latencies and intervals were analyzed in detail. The controls were 37 normal term infants and 35 very preterm non-BPD infants. RESULTS: Compared with normal term controls, BPD survivors showed significantly shortened I-III interval but significantly prolonged III-V interval and greater III-V/I-III interval ratio. Compared with very preterm non-BPD controls, BPD survivors showed a significant shortening in waves III latency and I-III interval, moderate prolonged III-V interval, and significantly greater III-V/I-III interval ratio. These differences were generally similar at all click rates used. The slopes of latency- and interval-click rate functions in BPD survivors did not differ significantly from the two control groups. CONCLUSIONS: Brainstem neural conduction in BPD survivors differed from normal term and age-matched non-BPD infants; neural maturation is accelerated in caudal brainstem regions but delayed in rostral regions. Neonatal BPD survivors are associated with differential maturation in neural conduction at caudal and rostral brainstem regions, which may constitute an important risk for postnatal neurodevelopment in BPD survivors. IMPACT: We found that brainstem neural conduction at PCA 57-58 weeks in neonatal BPD survivors differs from normal term and age-matched non-BPD infants. No major differences were found between normal term and very preterm non-BPD infants in brainstem auditory conduction. Neural conduction in BPD survivors is accelerated in caudal brainstem regions but delayed in rostral regions. Neonatal BPD survivors are associated with differential maturation in neural conduction at caudal and rostral brainstem regions. The abnormality may constitute an important risk for postnatal neurodevelopment in BPD survivors.

Mechanism of regulation of 'chromosome kissing' induced by Fob1 and its physiological significance.

Protein-mediated "chromosome kissing" between two DNA sites in trans (or in cis) is known to facilitate three-dimensional control of gene expression and DNA replication. However, the mechanisms of regulation of the long-range interactions are unknown. Here, we show that the replication terminator protein Fob1 of Saccharomyces cerevisiae promoted chromosome kissing that initiated rDNA recombination and controlled the replicative life span (RLS). Oligomerization of Fob1 caused synaptic (kissing) interactions between pairs of terminator (Ter) sites that initiated recombination in rDNA. Fob1 oligomerization and Ter-Ter kissing were regulated by intramolecular inhibitory interactions between the C-terminal domain (C-Fob1) and the N-terminal domain (N-Fob1). Phosphomimetic substitutions of specific residues of C-Fob1 counteracted the inhibitory interaction. A mutation in either N-Fob1 that blocked Fob1 oligomerization or C-Fob1 that blocked its phosphorylation antagonized chromosome kissing and recombination and enhanced the RLS. The results provide novel insights into a mechanism of regulation of Fob1-mediated chromosome kissing.

Impact of Lifetime Obesity on Urinary Incontinence in the Women's Health Initiative.

PURPOSE: We assessed the impact of lifetime obesity on the development of urinary incontinence (UI). MATERIALS AND METHODS: Using data from the Women's Health Initiative, we evaluated the cumulative impact of obesity over a postmenopausal woman's lifetime on the development of UI. Analyses using logistic models assessed the relationship between overweight/obesity duration and the development of UI during the Women's Health Initiative study at year 3. RESULTS: Of the 15,420 women aged 50-79 years, 4,568 (30.0%) developed UI by year 3. When controlling for covariates, the duration of overweight years (OWY) and obese years (OBY) was significantly associated with overall UI. The number of OWY was associated with an increased risk of developing UI postmenopausally (OR 1.17, 95% CI 1.13-1.22) compared to those with 0 OWY. The number of OBY was associated with a higher risk of developing UI postmenopausally (OR 1.28, 95% CI 1.18-1.39). Severity of UI was also associated with higher OWY/OBY. Compared to participants who maintained normal weight, those who gained weight from age 18 to 50 years were more likely to report increased UI (OR 1.26, 95% CI 1.16-1.37), as did those who remained overweight/obese (OR 1.27, 95% CI 1.04-1.55). Those who lost weight reported no difference in rates of any UI. CONCLUSIONS: Chronic, increased body mass index status is associated with an elevated risk of UI later in life. Symptom severity also appears to be worsened with duration of increased body mass index status. Weight management should be supported throughout one's lifetime, as it may impact UI in later stages of life.

Efficacy of Percutaneous Tibial Nerve Stimulation for Overactive Bladder in Women and Men at a Safety Net Hospital.

PURPOSE: We investigated efficacy and compliance related to percutaneous tibial nerve stimulation in patients treated for overactive bladder at a large, urban safety net hospital. MATERIALS AND METHODS: Consecutive patients who underwent percutaneous tibial nerve stimulation at Grady Memorial Hospital from May 2015 through January 2019 were included in our cohort and records were reviewed retrospectively. Primary outcomes of interest included self-reported urinary symptoms and episodes of urinary incontinence. Our secondary outcome of interest was patient compliance, defined as completion of 12 or more treatment sessions. Descriptive analysis and paired t-tests were performed. RESULTS: Of the 50 patients with a mean ± SD age of 59 ± 12 years 80% were black, 52% were male, 34% were uninsured and 54% subscribed to government insurance. Prior treatment included behavioral modification in 100% of cases, anticholinergics in 86% and mirabegron in 4%. Patients completed a mean of 10.7 ± 2.7 of the 12 planned weekly percutaneous tibial nerve stimulation treatments. Of the patients 70% completed all 12 weekly treatments and 77% of those who completed 12 treatments continued to maintenance treatment. After percutaneous tibial nerve stimulation treatment average symptoms improved across all metrics, including mean daytime frequency (from 11.0 to 6.6 episodes per day or -24.5%), nighttime frequency (from 4.8 to 2.5 episodes per night or -47.1%), urgency score (from 3.4 to 1.9 or -42.1%) and incontinence (from 1.6 to 0.4 episodes per day or -79.6%) (each p <0.001). A total of 43 patients (86%) reported symptom improvement. CONCLUSIONS: Percutaneous tibial nerve stimulation had favorable efficacy and compliance in a traditionally underserved patient population. This should be considered as a feasible modality to manage overactive bladder symptoms in patients in a similar demographic.

The Significance of Histologically "Large Normal" Parathyroid Glands in Primary Hyperparathyroidism.

INTRODUCTION: We investigated outcomes in a cohort of patients with a biochemical diagnosis of primary hyperparathyroidism (pHPT) undergoing surgery for asymptomatic disease or target organ damage, where a focussed or four-gland operation was undertaken and the histopathology only reported a "large normal" parathyroid gland (LNP). METHODS AND MATERIALS: Patients subjected to a parathyroidectomy for pHPT between 2012 and 2018 with a pathology of LNP were included. Patients with fat depletion or additional histological features of adenoma or hyperplasia in any of the resected glands were excluded. A control group was formed from 50 consecutive patients with the histological finding of adenoma or hyperplasia during the same study period. The primary outcome was biochemical normalisation of pHPT at 1-2 weeks and after 6 months post-operatively. RESULTS: Forty-eight LNP patients (2% of all parathyroidectomies) were included in the study group with 50 matched controls. LNP patients had a lower biochemical cure rate (81% vs. 98% P < 0.05) and a higher risk of recurrence (10% vs. 0%, P = 0.06). LNP patients had a milder form of pHPT (Ca2+ 2.63 vs. 2.68 P < 0.05) with a smaller PTH and Ca2+ drop post-operatively. For LNP patients with failure, a definite additional cause of pHPT was found in only two patients. CONCLUSION: This study highlights a controversial area in pHPT and reports LNP as a cause of pHPT. The biochemical analysis of this LNP group supports a benefit in resection in the setting of pHPT, although the risk of failure (persistence/recurrence) is higher than those with adenoma or hyperplasia. Stricter post-operative follow-up of LNP patients should be considered.

Total keratometry in intraocular lens power calculations in eyes with previous laser refractive surgery.

IMPORTANCE: Intraocular lens (IOL) calculations in post-refractive cases remain a concern. Our study identifies improved options for surgeons. BACKGROUND: To evaluate and compare the prediction accuracy of IOL power calculation methods after previous laser refractive surgery using standard keratometry (SK), measured posterior corneal astigmatism (PCA) and total keratometry (TK). DESIGN: Retrospective consecutive cohort. PARTICIPANTS: A total of 50 consecutive patients (72 eyes) at a private institution who underwent cataract surgery with prior laser refractive procedures. METHODS: Methods using SK included ASCRS mean, Barrett True-K no history, Haigis-L and Shammas IOL formulae. Barrett True-K using posterior values (True K TK), Haigis and Holladay 1 Double-K methods using TK were also assessed. Post-surgery refraction was undertaken at minimum 3 weeks following surgery. MAIN OUTCOME MEASURES: Arithmetic and absolute IOL refractive prediction errors, variances in mean arithmetic IOL prediction error, and percentage of eyes within ±0.25D, ±0.50D, ±0.75D and ±1.00D of refractive prediction errors were compared. RESULTS: The Barrett True-K (TK) provided the lowest mean refractive prediction error (RPE) and variance for both prior myopes and hyperopes undergoing cataract surgery. The Barrett True-K (TK) exhibited the highest percentages of eyes within ±0.50D, ±0.75D and ±1.00D of the RPE compared to other formulae for prior myopic patients. CONCLUSIONS AND RELEVANCE: Accuracy of IOL power calculations in post-laser eyes can be improved by the addition of posterior corneal values as measured by the IOLMaster 700. The use of total keratometry may supplement outcomes when no prior refraction history is known.

Dual roles of mitochondrial fusion gene FZO1 in yeast age asymmetry and in longevity mediated by a novel ATG32-dependent retrograde response.

The replicative lifespan of the yeast Saccharomyces cerevisiae models the aging of stem cells. Age asymmetry between the mother and daughter cells is established during each cell division, such that the daughter retains the capacity for self-renewal while this ability is diminished in the mother. The segregation of fully-functional mitochondria to daughter cells is one mechanism that underlies this age asymmetry. In this study, we have examined the role of mitochondrial dynamics in this phenomenon. Mitochondrial dynamics involve the processes of fission and fusion. Out of the three fusion and three fission genes tested, we have found that only FZO1 is required for the segregation of fully-functional mitochondria to daughter cells and in the maintenance of age asymmetry as manifested in the potential of daughters for a full replicative lifespan despite its deterioration in their mothers. The quality of mitochondria is determined by their turnover, and we have also discovered that deletion of FZO1 reduces mitophagy. Mitochondrial dysfunction elicits a compensatory retrograde response that extends replicative lifespan. Typically, the dysfunction that triggers this response encompasses energy production. The disruption of mitochondrial dynamics by deletion of FZO1 also activates the retrograde response to extend replicative lifespan. We call this novel pathway the mitochondrial dynamics-associated retrograde response (MDARR) because it is distinct in the signal proximal to the mitochondrion that initiates it. Furthermore, the MDARR engages the mitophagy receptor Atg32 on the mitochondrial surface, and we propose that this is due to the accumulation of Atg32-Atg11-Dnm1 complexes on the mitochondrion in the absence of Fzo1 activity. MDARR can be masked by the operation of the 'classic' retrograde response.

Purely wavelength- and amplitude-modulated quartz-enhanced photoacoustic spectroscopy.

We report here on a quartz-enhanced photoacoustic (QEPAS) sensor employing a quantum cascade laser (QCL) structure capable of operating in a pure amplitude or wavelength modulation configuration. The QCL structure is composed of three electrically independent sections: Gain, Phase (PS) and Master Oscillator (MO). Selective current pumping of these three sections allows obtaining laser wavelength tuning without changes in the optical power, and power modulation without emission wavelength shifts. A pure QEPAS amplitude modulation condition is obtained by modulating the PS current, while pure wavelength modulation is achieved by modulating simultaneously the MO and PS QCL sections and slowly scanning the DC current level injected in the PS section.

Natural genetic variation in yeast longevity.

The genetics of aging in the yeast Saccharomyces cerevisiae has involved the manipulation of individual genes in laboratory strains. We have instituted a quantitative genetic analysis of the yeast replicative lifespan by sampling the natural genetic variation in a wild yeast isolate. Haploid segregants from a cross between a common laboratory strain (S288c) and a clinically derived strain (YJM145) were subjected to quantitative trait locus (QTL) analysis, using 3048 molecular markers across the genome. Five significant, replicative lifespan QTL were identified. Among them, QTL 1 on chromosome IV has the largest effect and contains SIR2, whose product differs by five amino acids in the parental strains. Reciprocal gene swap experiments showed that this gene is responsible for the majority of the effect of this QTL on lifespan. The QTL with the second-largest effect on longevity was QTL 5 on chromosome XII, and the bulk of the underlying genomic sequence contains multiple copies (100-150) of the rDNA. Substitution of the rDNA clusters of the parental strains indicated that they play a predominant role in the effect of this QTL on longevity. This effect does not appear to simply be a function of extrachromosomal ribosomal DNA circle production. The results support an interaction between SIR2 and the rDNA locus, which does not completely explain the effect of these loci on longevity. This study provides a glimpse of the complex genetic architecture of replicative lifespan in yeast and of the potential role of genetic variation hitherto unsampled in the laboratory.

Incidence and Epidemiology of Intussusception among Infants in Ho Chi Minh City, Vietnam.

OBJECTIVE: To evaluate rates of intussusception hospitalization among infants in Vietnam before the introduction of rotavirus vaccine. STUDY DESIGN: Between 2009 and 2011, we identified intussusception hospitalizations among infants using the International Statistical Classification of Diseases and Related Health Problems, 10th Revision, Clinical Modification code K56.1 at 2 large pediatric hospitals in Ho Chi Minh City, Vietnam that treat most of the intussusception cases in the city. We reviewed all medical records to confirm a Brighton level 1 case definition for intussusception. RESULTS: We identified a total of 869 intussusception cases in Ho Chi Minh City during the 3-year study period, for an annual rate of 296 per 100,000 infants. The mean age of intussusception was ∼ 37 weeks (8.6 months), with <2% of the cases occurring before age 15 weeks. Cases of intussusception were observed year-round in these hospitals with no evident seasonal pattern. Ultrasonography was used to diagnose most cases (97%), and reduction was performed by air enema in >95% of the cases, with only 1% of cases at 1 hospital and 5% at the other hospital requiring surgical intervention. Ultrasound diagnosis was confirmed by an independent radiologist in 94% of a randomly selected group of intussusception cases at 1 of the 2 hospitals. No mortality was reported. CONCLUSION: Vietnam has a substantially higher rate of intussusception in children aged >15 weeks compared with most other regions of the world. Most of our cases were diagnosed by ultrasound, and only a small proportion required surgical intervention with no fatalities, suggesting that the higher rates may be related in part to better and earlier detection of intussusception.

Infants with neonatal Chronic Lung Disease are associated with delayed auditory conduction in the rostral brainstem after term.

AIMS: Very Low Birthweight (VLBW) infants with neonatal Chronic Lung Disease (CLD) have been found to have functional impairment of the brainstem auditory pathway at term. This study investigated the functional status of the brainstem auditory pathway in VLBW infants with CLD after term for any abnormality. METHODS: Fifty-two VLBW infants were recruited at 50 weeks of Postconceptional Age: 25 with neonatal CLD and 27 without CLD. None had any other major complications to minimize confounding effects. Brainstem Auditory Evoked Responses were studied at 21‒91/s click rates. RESULTS: Compared with those without CLD, VLBW infants with CLD had relatively shorter latencies of BAER waves I and III, associated with a slightly lower BAER threshold. Wave V latency and I‒V interpeak interval did not differ significantly between the two groups of infants. The I‒III interval in infants with CLD was shorter than in those without CLD at 91/s clicks. However, the III‒V interval was significantly longer than in those without CLD at all click rates (all p < 0.05). There were no significant differences in the amplitudes of BAER wave components between the two groups of infants. CONCLUSIONS: The main BAER abnormality in VLBW infants with CLD was a prolonged III‒V interval. Auditory conduction is delayed or impaired at more central regions of the brainstem in CLD infants. After term central auditory function is adversely affected by neonatal CLD. Monitoring post-term change is required to provide valuable information for post-term care of CLD infants.

Swept source optical coherence microscopy using a 1310 nm VCSEL light source.

We demonstrate high speed, swept source optical coherence microscopy (OCM) using a MEMS tunable vertical cavity surface-emitting laser (VCSEL) light source. The light source had a sweep rate of 280 kHz, providing a bidirectional axial scan rate of 560 kHz. The sweep bandwidth was 117 nm centered at 1310 nm, corresponding to an axial resolution of 13.1 µm in air, corresponding to 8.1 µm (9.6 µm spectrally shaped) in tissue. Dispersion mismatch from different objectives was compensated numerically, enabling magnification and field of view to be easily changed. OCM images were acquired with transverse resolutions between 0.86 µm - 3.42 µm using interchangeable 40X, 20X and 10X objectives with ~600 µm x 600 µm, ~1 mm x 1 mm and ~2 mm x 2 mm field-of-view (FOV), respectively. Parasitic variations in path length with beam scanning were corrected numerically. These features enable swept source OCM to be integrated with a wide range of existing scanning microscopes. Large FOV mosaics were generated by serially acquiring adjacent overlapping microscopic fields and combining them in post-processing. Fresh human colon, thyroid and kidney specimens were imaged ex vivo and compared to matching histology sections, demonstrating the ability of OCM to image tissue specimens.

High-precision, high-accuracy ultralong-range swept-source optical coherence tomography using vertical cavity surface emitting laser light source.

We demonstrate ultralong-range swept-source optical coherence tomography (OCT) imaging using vertical cavity surface emitting laser technology. The ability to adjust laser parameters and high-speed acquisition enables imaging ranges from a few centimeters up to meters using the same instrument. We discuss the challenges of long-range OCT imaging. In vivo human-eye imaging and optical component characterization are presented. The precision and accuracy of OCT-based measurements are assessed and are important for ocular biometry and reproducible intraocular distance measurement before cataract surgery. Additionally, meter-range measurement of fiber length and multicentimeter-range imaging are reported. 3D visualization supports a class of industrial imaging applications of OCT.

Suboptimal postnatal function of brainstem auditory pathway in late preterm infants who do not have major perinatal and postnatal complications.

OBJECTIVES: To examine postnatal functional status of the brainstem auditory pathway in late preterm infants and detect any postnatal auditory abnormality. METHODS: Thirty preterm infants born at 33-36 weeks gestation were studied three months after term. None had major perinatal and postnatal complications to minimize confounding effects. Brainstem auditory evoked responses were recorded with 21-91/s clicks. RESULTS: Compared with postnatal age-matched normal term infants, the late preterm infants did not manifest any major abnormalities in brainstem auditory evoked responses at conventionally used 21/s clicks. At higher click rates, however, the late preterm infants manifested a moderate prolongation in BAER wave V latency. All interpeak intervals tended to be prolonged at higher click rates. The I-V interval was significantly prolonged at 51/s and particularly at 91/s clicks. Both the I-III and III-V intervals were significantly prolonged at 91/s. The late preterm infants also manifested reduced amplitudes of BAER waves III and V at most click rates. CONCLUSION: The central components of the brainstem auditory evoked responses were abnormal at higher click rates three months after term in the late preterm infants. Postnatal brainstem auditory function is suboptimal in late preterm infants without major complications. This suboptimal brainstem auditory function may not be clearly shown at term or an earlier stage, but can be shown later. Late preterm infants, although they may not have major complications, should be followed for later auditory development, providing valuable information for improving postnatal care.

Optical coherence microscopy for deep tissue imaging of the cerebral cortex with intrinsic contrast.

In vivo optical microscopic imaging techniques have recently emerged as important tools for the study of neurobiological development and pathophysiology. In particular, two-photon microscopy has proved to be a robust and highly flexible method for in vivo imaging in highly scattering tissue. However, two-photon imaging typically requires extrinsic dyes or contrast agents, and imaging depths are limited to a few hundred microns. Here we demonstrate Optical Coherence Microscopy (OCM) for in vivo imaging of neuronal cell bodies and cortical myelination up to depths of ~1.3 mm in the rat neocortex. Imaging does not require the administration of exogenous dyes or contrast agents, and is achieved through intrinsic scattering contrast and image processing alone. Furthermore, using OCM we demonstrate in vivo, quantitative measurements of optical properties (index of refraction and attenuation coefficient) in the cortex, and correlate these properties with laminar cellular architecture determined from the images. Lastly, we show that OCM enables direct visualization of cellular changes during cell depolarization and may therefore provide novel optical markers of cell viability.