Understanding the caregiving experiences of Asian Indian, Chinese, Korean, and Vietnamese American family care partners of persons living with dementia.

OBJECTIVES: Disparities impacting dementia health care exist in racial/ethnic minority groups, including Asian Americans, an understudied population in Alzheimer's disease and related dementias. The qualitative study explored caregiving experiences and potential cultural influences among Asian Indian, Chinese, Korean, and Vietnamese family care partners of persons living with dementia. METHODS: We conducted focus groups and individual interviews with 32 care partners from these four Asian subgroups using Zoom, WeChat, or telephone. RESULTS: Four themes emerged from the data: (1) Family obligations influencing caregiving decisions; (2) Evolving challenges related to dementia caregiving; (3) Caregiving burdens/negative impacts from caregiving (relationship burdens and emotional distress); and (4) Coping with their situation in their own ways (cognitive, behavioral, and social strategies).Conclusion: Cultural values (e.g. familism or filial piety) played a significant role in caregiving decisions and experiences. There was a need to raise public awareness of dementia and create culturally and linguistically appropriate training programs for this population.

Unusual local epidemic of paediatric respiratory syncytial virus during a time of global pandemic.

BACKGROUND: Western Australia (WA) public health measures to eradicate SARS-CoV-2 resulted in a secondary reduction in paediatric respiratory syncytial virus (RSV) admissions. Following an absent expected 2020 winter peak, RSV-positive admissions surged during the summer of 2020. AIM: This report examines the number of RSV-positive admissions and severities across 36 months to better understand this out-of-season epidemic. METHODS: A retrospective observational study was performed assessing the number and severity of RSV-related respiratory hospitalisations at a peripheral paediatric centre from March 2018 to February 2021. Data were extracted from the hospital clinical database. RESULTS: The total number of included participants was n = 294. The total number of RSV hospitalisations in SY (study year) 2018 (March 2018 to February 2019), SY 2019 (March 2019 to February 2020) and SY 2020 (March 2020 to February 2021) was 67, 98 and 129, respectively. Prior to SARS-CoV-2, RSV hospitalisations were highest during the winter months. In SY 2020, there were 0 RSV hospitalisations during winter, while 101 admissions in the following summer season. The proportion of admissions requiring respiratory support was significantly reduced in SY 2020 (34.1%) compared to SY 2018 (46.9%, P = 0.050) and SY 2019 (55.2%, P = 0.004). The median length of stay (LOS) in 2020 was 2.0 which was significantly reduced from 2018 and 2019 which was 3.0, P = 0.001; and 3.0, P < 0.001, respectively. CONCLUSION: Following a period of RSV absence, there was an unprecedented surge in admission, however, with lower severity and shorter LOS.

A Single Source, Scalable Route for Direct Isolation of Earth-Abundant Nanometal Carbide Water-Splitting Electrocatalysts.

Single-phase MxCs (M = Fe, Co, and Ni) were prepared by solvothermal conversion of Prussian blue single source precursors. The single source precursor is prepared in water, and the conversion process is carried out in alkylamines at reaction temperatures above 200 °C. The reaction is scalable using a commercial source of Fe-PB. High-resolution transmission electron microscopy, X-ray photoelectron microscopy, and powder X-ray diffraction confirm that carbides have thin oxide termination but lack graphitic surfaces. Electrocatalytic activity reveals that Fe3C and Co2C are oxygen evolution reaction electrocatalysts, while Ni3C is a bifunctional [OER and hydrogen evolution reaction (HER)] electrocatalyst.

Association of CT findings in patients with hemoperitoneum due to ruptured ovarian cysts with subsequent intervention.

PURPOSE: Hemoperitoneum caused by ovarian cyst rupture may necessitate intervention. The literature is lacking in descriptions of CT findings that help guide patient management. The purpose of this study is to consider CT findings associated with a need for intervention (surgical or interventional radiology management) versus conservative treatment (observation, pain management, and blood transfusions). METHODS: Two radiologists retrospectively and independently reviewed 103 CTs of pre-menopausal women who presented with acute hemoperitoneum related to ruptured ovarian cysts between January 2010 and January 2019. The following imaging features were assessed: ovarian cyst characteristics, sentinel clot, contrast extravasation, and hemoperitoneum size. Findings were correlated with patient demographics, clinical parameters, and management with surgery/interventional radiology procedure (intervention group) versus conservative management (conservative group). RESULTS: Of the 103 patients with hemoperitoneum from cyst rupture, 16% (n = 16) required intervention, and 84% underwent conservative treatment (n = 87). Length of stay (p = .008) was higher in the intervention group. Statistically significant CT findings in the intervention versus conservative group included (p-value reader 1/p-value reader 2) greatest AP dimension of hemoperitoneum (p = .001/p = 0.02), posterior cul-de-sac AP dimension (p = 0.03/p = .006), total cul-de-sac AP dimension (p = .002/p = .007), and number of spaces with hemoperitoneum (p = .01/p = .02). There was good to excellent inter-reader agreement for these findings (ICC 0.68-0.91). Active contrast extravasation was significant for one reader (p = .02) with poor inter-reader agreement (ICC 0.36). In utilizing ROC curves, thresholds of 107 mm (greatest axial AP dimension of hemoperitoneum) yielded a sensitivity and specificity of 0.81 and 0.62 for reader 1 and 0.69 and 0.55 for reader 2; 45 mm (posterior cul-de-sac AP dimension) yielded a sensitivity and specificity of 0.75 and 0.63 for reader 1 and 0.94 and 0.49 for reader 2; 70 mm (total cul-de-sac AP dimension) yielded a sensitivity and specificity of 0.75 and 0.64 for reader 1 and 0.75 and 0.50 for reader 2; and greater than 5 spaces yielded a sensitivity and specificity of 0.75 and 0.58 for reader 1 and 0.69 and 0.70 for reader 2. CONCLUSION: CT findings associated with intervention in hemoperitoneum due to ovarian cyst rupture include size of hemoperitoneum, number of abdominopelvic spaces with hemoperitoneum, and contrast extravasation.

Chest radiograph at admission predicts early intubation among inpatient COVID-19 patients.

OBJECTIVE: The 2019 Coronavirus (COVID-19) results in a wide range of clinical severity and there remains a need for prognostic tools which identify patients at risk of rapid deterioration and who require critical care. Chest radiography (CXR) is routinely obtained at admission of COVID-19 patients. However, little is known regarding correlates between CXR severity and time to intubation. We hypothesize that the degree of opacification on CXR at time of admission independently predicts need and time to intubation. METHODS: In this retrospective cohort study, we reviewed COVID-19 patients who were admitted to an urban medical center during March 2020 that had a CXR performed on the day of admission. CXRs were divided into 12 lung zones and were assessed by two blinded thoracic radiologists. A COVID-19 opacification rating score (CORS) was generated by assigning one point for each lung zone in which an opacity was observed. Underlying comorbidities were abstracted and assessed for association. RESULTS: One hundred forty patients were included in this study and 47 (34%) patients required intubation during the admission. Patients with CORS ≥ 6 demonstrated significantly higher rates of early intubation within 48 h of admission and during the hospital stay (ORs 24 h, 19.8, p < 0.001; 48 h, 28.1, p < 0.001; intubation during hospital stay, 6.1, p < 0.0001). There was no significant correlation between CORS ≥ 6 and age, sex, BMI, or any underlying cardiac or pulmonary comorbidities. CONCLUSIONS: CORS ≥ 6 at the time of admission predicts need for intubation, with significant increases in intubation at 24 and 48 h, independent of comorbidities. KEY POINTS: • Chest radiography at the time of admission independently predicts time to intubation within 48 h and during the hospital stay in COVID-19 patients. • More opacities on chest radiography are associated with several fold increases in early mechanical ventilation among COVID-19 patients. • Chest radiography is useful in identifying COVID-19 patients whom may rapidly deteriorate and help inform clinical management as well as hospital bed and ventilation allocation.

The Indications for Elective Neck Dissection in T1N0M0 Oral Cavity Squamous Cell Carcinoma.

PURPOSE: The management of the clinically node-negative neck in T1 oral cavity squamous cell carcinoma (SCC) is controversial. The purpose of this study was to investigate tumor characteristics of surgically managed patients with T1N0 oral cavity SCC and determine the possible benefits of elective neck dissection (END). MATERIALS AND METHODS: A retrospective cohort study was conducted assessing outcomes for patients with stage I oral SCC at Waikato Hospital, New Zealand, between 2008 and 2018. Clinical staging was based on the American Joint Committee on Cancer Cancer Staging Manual, 8th Edition. Patients with T1N0 SCC either had an END or had the neck observed. These data were used to determine the rate of occult nodal disease, recurrence rate, and survival. Data collected included patient demographics, location, tumor characteristics including differentiation, depth of invasion (DOI), perineural invasion (PNI), lymphovascular invasion, closest histologic margin, management of the neck, the number of pathologic lymph nodes, adjuvant treatment, recurrence, and survival. RESULTS: A total of 70 patients were included in the study (40 male, 30 female; age range 30 to 91; mean age 65 years). Twenty-seven (38.6%) patients underwent END, whereas 43 patients (61.4%) were observed. Occult nodal metastases were diagnosed in 6 of 27 (22.2%) patients who underwent END. Regional relapse occurred in 7 of 43 (16.3%) patients who were observed. Risk factors for nodal disease included increasing DOI ≥ 3 mm (P = .049), poor tumor differentiation (P = .003), and presence of PNI (P = .002). Negative prognostic factors for overall survival included male gender (P = .02, hr = 3.55, CI for HR (1.18, 10.65)), presence of PNI (P = .001, hr = 4.52, CI for HR (1.77, 11.57)), and locoregional recurrence (P < .005, hr = 6.55, CI for HR (2.69, 15.98)). Six of the 7 tumors that relapsed in the neck after observation had a primary tumor DOI < 3 mm. CONCLUSIONS: There is little data published for management outcomes of the node-negative neck in stage I oral squamous cell carcinoma. Given salvage neck dissection carries a poorer prognosis, END should be recommended for all T1N0 oral SCC with DOI ≥ 3 mm. In cases of DOI < 3 mm undergoing primary ablation only, a staging neck dissection as a second procedure should be considered in the presence of poor tumor differentiation or PNI on final histology.

Improved Outcomes of Orbital Reconstruction With Intraoperative Imaging and Rapid Prototyping.

PURPOSE: Rapid prototyping and intraoperative computed tomography (CT) are increasingly used in orbital reconstruction when placement of implants is indicated and accurate anatomic restoration is mandatory. The purpose of this study was to review the outcomes of orbital reconstructions at a single institution and the influence of intraoperative CT and rapid prototyping on the rate of return to the operating theater. MATERIALS AND METHODS: A retrospective cohort analysis was performed from 2013 through 2016 to assess whether rapid prototyping and intraoperative imaging were used and the need for further revision surgery. Clinical notes were reviewed and data were collected for patient gender, age, fracture pattern, preoperative diplopia, and enophthalmos. Also noted were whether rapid prototyping and intraoperative imaging were used, the number of "spins" required, plating systems, postoperative diplopia and enophthalmos, restoration of orbital form, and the need for further surgical intervention. Patients were excluded if no orbital implants were inserted or if they were lost to follow-up. RESULTS: Three hundred thirty-one cases of orbital trauma were reviewed (248 male and 83 female patients; age range, 7 to 96 yr; mean age, 37.5 yr). In total, 154 orbital reconstructions were performed from 2013 through 2016. Five cases required a return to the operating theater for implant revision. All 5 cases did not use intraoperative imaging (P = .0016), and 4 did not have a rapid prototype bio-model (P = .006). Twenty-five of 110 cases (22.7%) using intraoperative CT required intraoperative revision. CONCLUSION: The present study shows improved outcomes for patients treated for orbital fractures when intraoperative imaging and rapid prototyping bio-modeling are used. As a result, postoperative imaging and the morbidity of revision surgery can be avoided. These technologies should be available and considered standard of care to any surgeon performing reconstruction of orbital fractures.

Enabling Homochirality and Hydrothermal Stability in Zn4O-Based Porous Crystals.

The [Zn4O]6+ cluster is well-known to form the archetypal MOF-5 topology with dicarboxylate ligands. Here we report two new materials (CPM-300 and -301) that show dramatic alteration of topological and chemical behaviors of [Zn4O]6+ clusters. In CPM-300, [Zn4O]6+ untypically forms the MIL-88/MOF-235 type framework with a small pentane-ring-based chiral dicarboxylate. In contrast, in CPM-301, when mediated by [Zn9(btz)12]6+ clusters (btz = benzotriazolate), the MOF-5 topology is regenerated with the same chiral ligand, albeit with alternating [Zn4O]6+ and [Zn9(btz)12]6+ clusters. Importantly, both CPM-300 and CPM-301 are homochiral, hydrothermally stable in boiling water and alcohol, and thermally stable to 440 °C or higher. It is concluded that small methyl groups on the chiral ligand is sufficiently powerful to shield [Zn4O]6+ clusters from degradation by water, even at high temperatures. These results reveal a promising platform for the development of a new class of cluster-based homochiral and hydrothermally stable porous materials.

Chiral Isocamphoric Acid: Founding a Large Family of Homochiral Porous Materials.

Homochiral metal-organic frameworks (MOFs) are an important class of chiral solids with potential applications in chiral recognition; however, relatively few are available. Of great importance is the availability of low-cost, racemization-resistant, and versatile enantiopure building blocks. Among chiral building blocks, d-camphoric acid is highly prolific, yet, its trans-isomer, l-isocamphoric acid, has remained unknown in the entire field of solid-state materials. Its rich yet totally untapped synthetic and structural chemistry has now been investigated through the synthesis of a large family of homochiral metal isocamphorates. The first observation of diastereoisomerism in isostructural MOFs is presented. Isocamphorate has a powerful ability to create framework topologies unexpected from common inorganic building blocks, and isocamphoric acid should allow access to hundreds of new homochiral materials.

Multivariable Modular Design of Pore Space Partition.

Pore space partition, especially the one using C3-symmetric 2,4,6-tri(4-pyridyl)-1,3,5-triazine as pore-partition agent in MIL-88 type (the acs net), has been shown to dramatically enhance CO2 uptake to near-record values. The continued advance in property engineering via pore space partition would depend on intelligent design of both framework components and pore-partition agent. Here, we report a new advance in the design of pore-partition agent by demonstrating a symmetry-guided pathway to develop a large variety of di- and trinuclear 1,2,4-triazolate-based clusters for use as pore-partition agent. The use of metal-organic clusters (instead of organic ligands) as pore-partition agent gives rise to many new pore-partitioned materials with huge compositional variety. The full assembly involves the simultaneous formation of two separate coordination architectures (i.e., the 3-D acs framework and 0-D triazolate clusters) and the eventual welding between the acs framework and triazolate clusters. The wide range of new compositions and structures provides a high degree of tunability in gas sorption properties.

SPACA7 is a novel male germ cell-specific protein localized to the sperm acrosome that is involved in fertilization in mice.

Sperm acrosome associated 7 (SPACA7) is a novel protein of unknown function with no homology to any known protein. Spaca7 transcripts are detected only in testis and predict a 158-residue mature polypeptide with one potential N-glycosylation site and no cysteines. Orthologs are present in various species, including mice and humans. We developed a polyclonal antibody to mouse SPACA7 to study its expression and function. Western blotting and immunofluorescence microscopy detected SPACA7 only in testis, and it was detected in testis starting at Postnatal Day 21 and into adulthood. Immunofluorescence staining of testicular germ cells detected weak SPACA7 expression as early as zygotene spermatocytes. Higher expression was observed in round spermatids, where SPACA7 was localized to a perinuclear spot adjacent to the Golgi and to the acrosome of elongating spermatids and spermatozoa. Immunogold electron microscopy demonstrated that SPACA7 is localized within the proacrosomal granule of round spermatids and the acrosome of spermatozoa. Finally, we showed that SPACA7 was retained within the acrosome of epididymal sperm and was released upon the acrosome reaction. To assess if SPACA7 was involved in fertilization, in vitro fertilization assays in the presence of anti-SPACA7 IgG were performed. Anti-SPACA7 inhibited fertilization of cumulus-intact eggs and prominently delayed cumulus dispersal. However, anti-SPACA7 did not inhibit fertilization of cumulus-free eggs. Our findings indicate that release of SPACA7 from the acrosome accelerates cumulus dispersal and facilitates fertilization via unknown mechanisms. This study is the first to document the expression of endogenous SPACA7 and a function for this novel acrosomal protein.

Impaired sperm maturation in RNASE9 knockout mice.

Ribonuclease, RNase A family, 9 (RNASE9) is a ribonuclease A superfamily member that is expressed only in the epididymis. It is a small, secreted polypeptide, it lacks ribonuclease activity, and its function(s) is unknown. However, epididymis-specific expression suggests a role in sperm maturation. We generated Rnase9(-/-) mice to study RNASE9 function in vivo. We confirm that RNASE9 expression is restricted to the epididymis. Within the epididymis, RNASE9 is first detected in midcaput, persists through the distal caput and corpus, and wanes in the cauda. Rnase9(-/-) mice are born at the expected Mendelian ratio, have normal postnatal growth and development, and have no outwardly apparent phenotype. Spermatogenesis is normal, and Rnase9-null sperm are morphologically normal. Rnase9(-/-) males have normal fertility in unrestricted mating trials, and fertilization rates in in vitro fertilization assays are indistinguishable from wild-type mice. Visual observations coupled with analyses of sperm velocities shortly after swim out from the corpus shows that motility of Rnase9-null sperm is significantly impaired. However, no differences between wild-type and Rnase9-null sperm are detected by computer-assisted sperm analysis 10-90 min after sperm isolation from the corpus or cauda. Assessment of capacitation-dependent signaling pathways in Rnase9-null sperm showed that, while levels of tyrosine phosphorylation of sperm proteins were normal, there was decreased phosphorylation of protein kinase A substrates upon capacitation compared to wild-type mice. In conclusion, RNASE9 is dispensable for fertility, but the absence of RNASE9 during epididymal transit results in impaired sperm maturation.

Risk factors for permanent injury of inferior alveolar and lingual nerves during third molar surgery.

PURPOSE: The purpose of this study was to assess the incidence of and risk factors for permanent neurologic injuries to the inferior alveolar nerve (IAN) or lingual nerve (LN) after the removal of third molars. This report also describes the use of a Clinical Incident Review (CIR) process, allowing close monitoring of all patients with neurologic injuries as a result of dentoalveolar surgery. MATERIALS AND METHODS: A database associated with a CIR process at the Royal Dental Hospital of Melbourne from January 2006 through December 2009 was assessed. Factors assessed included gender, age, operator class, method of anesthesia, spacial relation, depth of impaction, ramus relation, proximity of the IAN on orthopantomogram, cone-beam computed tomographic usage, and side of injury. RESULTS: During this 4-year period, 11,599 lower third molars were removed in 6,803 patients. The incidence of an IAN injury was 0.68%, and the incidence of an LN injury was 0.15%. Important risk factors for permanent IAN injury were increasing age, surgery performed by staff dentists, type of anesthesia, and mesioangular impactions. The mean time of complete resolution was 4.3 months. No factors were found to statistically increase the risk of LN injury, although most injuries were seen in patients with a distoangular impaction. CONCLUSION: The overall incidences of IAN and LN injuries were low. Some risk factors for permanent IAN nerve injury were identified. Important risk factors for permanent IAN injury were increasing age (≥25 yr old), surgery performed by staff dentists, surgery under general anesthesia, and mesioangular impaction. No factors were found to statistically increase the risk of LN injury.

Salivary gland tumours: an epidemiological review of non-neoplastic and neoplastic pathology.

Salivary gland tumours (SGT) demonstrate geographical variation. The primary objective of this study was to determine the types, frequency, distribution, and demographics of non-neoplastic and neoplastic salivary gland pathology at Waikato Hospital, New Zealand (NZ) over a 10-year period. Following this we conducted a 10-year retrospective review of SGT epidemiology from international literature. In total 825 patients were identified, 31% (256/825) with non-neoplastic salivary gland pathology, 34% (284/825) with benign neoplastic pathology, 14% (118/825) with primary malignant lesions, 18% (146/825) with metastatic SGTs, and 3% (21/825) with lymphoma. Patients had a mean (range) age of 58 (3-102) years, were predominantly male (58%, 476/825), and NZ European (65%, 536/825). Tumours were most prevalent in the parotid gland (85%, 484/569), of which 44% (211/484) were malignant. Pleomorphic adenoma was the most common benign (71%, 203/284) and overall (36%, 203/569) tumour, while mucoepidermoid carcinoma (25%, 29/118) and squamous cell carcinoma (SCC) (73%, 106/146) were the most common primary malignant and metastatic SGTs, respectively. Our literature review identified 18 studies consisting of 33,933 patients, of whom 71% (24,013/33,933) had benign SGTs. Pleomorphic adenoma (68%, 16404/24013) and mucoepidermoid carcinoma (29%, 2826/9621) were the most common benign and malignant SGTs, respectively. Low numbers of non-neoplastic and metastatic SGTs were reported in the literature. This research provides a greater understanding of differences in their global distribution. Consistent with previous literature, pleomorphic adenoma and mucoepidermoid carcinoma were the most common benign and malignant SGTs. In NZ, we found high rates of malignant SCC to the parotid gland, consistent with the epidemiology of non-melanoma skin cancer in the country.

Genomic Landscape of Circulating-Tumor DNA in a Diverse Cohort of Metastatic Breast Cancer Patients.

INTRODUCTION: Breast cancer is the most prevalent cancer and the second leading cause of cancer death among women in the United States. Liquid biopsy is becoming a more commonly accepted method in clinical practice. Thus, there is a need to investigate ways to utilize circulating-tumor DNA (ctDNA) in metastatic breast cancer (mBC). The primary objective of this study was to characterize the genomic landscape of ctDNA in a diverse patient population and across different subtypes of mBC. METHODS: We analyzed the ctDNA profile in patients (n = 45) with mBC who received a Guardant360 liquid biopsy test. Patient demographics, age at diagnosis, race, subtype, and mutations were included in the analysis. RESULTS: The majority of patients (n = 39, 86.7%) had at least one gene alteration detected in their liquid biopsy. We found no statistically significant differences in genomic landscape according to race. However, there were differences seen in tumor genomics according to age and subtype. Postmenopausal patients were more likely to have detectable disease on liquid biopsy compared to premenopausal patients (p = 0.001). Mutations in ESR1 (n = 10) and PIK3CA (n = 8) were more commonly seen in hormone positive (HR+) mBC, where known tailored treatment options are available (i.e., fulvestrant and alpelisib respectively). The most common alterations detected include TP53 (n = 22) followed by PIK3CA (n = 15), ESR1 (n = 11), CCND1 (n = 7), and ERBB2 (n = 7). CONCLUSION: Liquid biopsies are effective tools that can reveal clinically relevant information including mutational status and therapeutic options.

Electrocatalytic activity and surface oxide reconstruction of bimetallic iron-cobalt nanocarbide electrocatalysts for the oxygen evolution reaction.

For renewable energy technology to become ubiquitous, it is imperative to develop efficient oxygen evolution reaction (OER) electrocatalysts, which is challenging due to the kinetically and thermodynamically unfavorable OER mechanism. Transition metal carbides (TMCs) have recently been investigated as desirable OER pre-catalysts, but the ability to tune electrocatalytic performance of bimetallic catalysts and understand their transformation under electrochemical oxidation requires further study. In an effort to understand the tunable TMC material properties for enhancing electrocatalytic activity, we synthesized bimetallic FeCo nanocarbides with a complex mixture of FeCo carbide crystal phases. The synthesized FeCo nanocarbides were tuned by percent proportion Fe (i.e. % Fe), and analysis revealed a non-linear dependence of OER electrocatalytic activity on % Fe, with a minimum overpotential of 0.42 V (15-20% Fe) in alkaline conditions. In an effort to understand the effects of Fe composition on electrocatalytic performance of FeCo nanocarbides, we assessed the structural phase and electronic state of the carbides. Although we did not identify a single activity descriptor for tuning activity for FeCo nanocarbides, we found that surface reconstruction of the carbide surface to oxide during water oxidation plays a pivotal role in defining electrocatalytic activity over time. We observed that a rapid increase of the (FexCo1-x)2O4 phase on the carbide surface correlated with lower electrocatalytic activity (i.e. higher overpotential). We have demonstrated that the electrochemical performance of carbides under harsh alkaline conditions has the potential to be fine-tuned via Fe incorporation and with control, or suppression, of the growth of the oxide phase.

Vaginal bacteria elicit acute inflammatory response in fallopian tube organoids: a model for pelvic inflammatory disease.

Objective: To facilitate in vitro mechanistic studies in pelvic inflammatory disease (PID) and subsequent tubal factor infertility, as well as ovarian carcinogenesis, we sought to establish patient tissue derived fallopian tube (FT) organoids and to study their inflammatory response to acute vaginal bacterial infection. Design: Experimental study. Setting: Academic medical and research center. Patients: FT tissues were obtained from four patients after salpingectomy for benign gynecological diseases. Interventions: We introduced acute infection in the FT organoid culture system by inoculating the organoid culture media with two common vaginal bacterial species, Lactobacillus crispatus and Fannyhessea vaginae . Main Outcome Measures: The inflammatory response elicited in the organoids after acute bacterial infection was analyzed by the expression profile of 249 inflammatory genes. Results: Compared to the negative controls that were not cultured with any bacteria, the organoids cultured with either bacterial species showed multiple differentially expressed inflammatory genes. Marked differences were noted between the Lactobacillus crispatus infected organoids and those infected by Fannyhessea vaginae . Genes from the C-X-C motif chemokine ligand (CXCL) family were highly upregulated in F. vaginae infected organoids. Flow cytometry showed that immune cells quickly disappeared during the organoid culture, indicating the inflammatory response observed with bacterial culture was generated by the epithelial cells in the organoids. Conclusion: Patient tissue derived FT organoids respond to acute bacterial infection with upregulation of inflammatory genes specific to different vaginal bacterial species. FT organoids is a useful model system to study the host-pathogen interaction during bacterial infection which may facilitate mechanistic investigations in PID and its contribution to tubal factor infertility and ovarian carcinogensis.

State of the Art Imaging of Osteoporosis.

Osteoporosis is a common disease, particularly prevalent in geriatric populations, which causes significant worldwide morbidity due to increased bone fragility and fracture risk. Currently, the gold-standard modality for diagnosis and evaluation of osteoporosis progression and treatment relies on dual-energy x-ray absorptiometry (DXA), which measures bone mineral density (BMD) and calculates a score based upon standard deviation of measured BMD from the mean. However, other imaging modalities can also be used to evaluate osteoporosis. Here, we review historical as well as current research into development of new imaging modalities that can provide more nuanced or opportunistic analyses of bone quality, turnover, and density that can be helpful in triaging severity and determining treatment success in osteoporosis. We discuss the use of opportunistic computed tomography (CT) scans, as well as the use of quantitative CT to help determine fracture risk and perform more detailed bone quality analysis than would be allowed by DXA . Within magnetic resonance imaging (MRI), new developments include the use of advanced MRI techniques such as quantitative susceptibility mapping (QSM), magnetic resonance spectroscopy, and chemical shift encoding-based water-fat MRI (CSE-MRI) to enable clinicians improved assessment of nonmineralized bone compartments as well as a way to longitudinally assess bone quality without the repeated exposure to ionizing radiation. Within ultrasound, development of quantitative ultrasound shows promise particularly in future low-cost, broadly available screening tools. We focus primarily on historical and recent developments within radiotracer use as applicable to osteoporosis, particularly in the use of hybrid methods such as NaF-PET/CT, wherein patients with osteoporosis show reduced uptake of radiotracers such as NaF. Use of radiotracers may provide clinicians with even earlier detection windows for osteoporosis than would traditional biomarkers. Given the metabolic nature of this disease, current investigation into the role molecular imaging can play in the prediction of this disease as well as in replacing invasive diagnostic procedures shows particular promise.

Sugar transporter Slc37a2 regulates bone metabolism in mice via a tubular lysosomal network in osteoclasts.

Osteoclasts are giant bone-digesting cells that harbor specialized lysosome-related organelles termed secretory lysosomes (SLs). SLs store cathepsin K and serve as a membrane precursor to the ruffled border, the osteoclast's 'resorptive apparatus'. Yet, the molecular composition and spatiotemporal organization of SLs remains incompletely understood. Here, using organelle-resolution proteomics, we identify member a2 of the solute carrier 37 family (Slc37a2) as a SL sugar transporter. We demonstrate in mice that Slc37a2 localizes to the SL limiting membrane and that these organelles adopt a hitherto unnoticed but dynamic tubular network in living osteoclasts that is required for bone digestion. Accordingly, mice lacking Slc37a2 accrue high bone mass owing to uncoupled bone metabolism and disturbances in SL export of monosaccharide sugars, a prerequisite for SL delivery to the bone-lining osteoclast plasma membrane. Thus, Slc37a2 is a physiological component of the osteoclast's unique secretory organelle and a potential therapeutic target for metabolic bone diseases.

Sole abnormalities of chromosome 7 in myeloid malignancies: spectrum, histopathologic correlates, and prognostic implications.

Among 6,565 consecutive abnormal cytogenetic reports at our institution, 3,192 (49%) constituted sole abnormalities, of which 230 (7%) involved chromosome 7: monosomy 7 (n = 98), 7q- (n = 51), der(1;7)(q10;p10) (n = 44), balanced translocations (n = 15), ring 7 (n = 13), and 7p- (n = 9). The most frequent histopathologic correlates were myelodysplastic syndromes (MDS; 28%), acute myeloid leukemia (AML; 17%), secondary or therapy-related MDS/AML (13%), primary myelofibrosis (PMF; 7%), and chronic myelomonocytic leukemia (6%). Monosomy 7 was the most frequent in each one of these disease categories except PMF where 7q- was more frequent. In primary MDS, patients with der(1;7)(q10;p10) (n = 13), compared to those with monosomy 7 (n = 30) or 7q- (n = 15), were less likely (P = 0.04) to display excess blasts or multilineage dysplasia but overall and leukemia-free survival adjusted for these variables revealed no significant difference between the three groups (P = 0.57 and 0.81, respectively). The current study does not prognostically distinguish monosomy 7 from 7q- or der(1;7), in MDS.