Inverse genetics tracing the differentiation pathway of human chondrocytes.

OBJECTIVE: Mammalian somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) via the forced expression of Yamanaka reprogramming factors. However, only a limited population of the cells that pass through a particular pathway can metamorphose into iPSCs, while the others do not. This study aimed to clarify the pathways that chondrocytes follow during the reprogramming process. DESIGN: The fate of human articular chondrocytes under reprogramming was investigated through a time-coursed single-cell transcriptomic analysis, which we termed an inverse genetic approach. The iPS interference technique was also employed to verify that chondrocytes inversely return to pluripotency following the proper differentiation pathway. RESULTS: We confirmed that human chondrocytes could be converted into cells with an iPSC phenotype. Moreover, it was clarified that a limited population that underwent the silencing of SOX9, a master gene for chondrogenesis, at a specific point during the proper transcriptome transition pathway, could eventually become iPSCs. Interestingly, the other cells, which failed to be reprogrammed, followed a distinct pathway toward cells with a surface zone chondrocyte phenotype. The critical involvement of cellular communication network factors (CCNs) in this process was indicated. The idea that chondrocytes, when reprogrammed into iPSCs, follow the differentiation pathway backward was supported by the successful iPS interference using SOX9. CONCLUSIONS: This inverse genetic strategy may be useful for seeking candidates for the master genes for the differentiation of various somatic cells. The utility of CCNs in articular cartilage regeneration is also supported.

The Mental Health Effects and Experiences of Breastfeeding Decision-Making Among Postpartum Women Living with HIV.

Prior to January 2023, women living with HIV (WLWH) in the United States (US) were discouraged from breastfeeding due to the potential risk of mother-to-child HIV transmission through breastfeeding. Lack of breastfeeding decision-making and experience among WLWH may negatively affect maternal mental health. We implemented a quality improvement initiative to screen WLWH for postpartum depression (PPD), evaluate their attitudes toward breastfeeding, and assess their experience with breastfeeding decision-making. We collected quantitative data from WLWH using a voluntary, self-administered 6-item breastfeeding decision-making and experience survey (administered 1 month postpartum) and a 10-item Edinburgh Postnatal Depression Scale (EPDS, negative = 0-9; administered 1 and 4 months postpartum) tool. We conducted descriptive statistics and cross tabulation analysis. We analyzed 106 WLWH (93.4% non-Hispanic Black/African American; mean age 33.1 years; 82.1% HIV RNA < 200 copies/mL). One in five (19.1%) WLWH had a positive baseline EPDS screen, with the mean EPDS scores decreasing from 5.3 ± 5.4 (baseline) to 4.6 ± 4.8 (follow-up). Among 55 WLWH who provided baseline and follow-up EPDS scores, only 3/13 with a positive baseline EPDS screen had resolved depressive symptoms at follow-up. Over one-third (37.7%) of WLWH indicated feeling "sadness" when asked whether lack of breastfeeding negatively affected their feelings or emotions. Over half of WLWH (51.9%) were aware of the US breastfeeding recommendations, but the majority (60.4%) had never discussed breastfeeding options with a medical provider. Improved provider-patient discussions on infant feeding options among WLWH is needed to increase awareness of breastfeeding choices and promote informed, autonomous breastfeeding decision-making among WLWH.

Development of an antibody cocktail for treatment of Sudan virus infection.

Antibody-based therapies are a promising treatment option for managing ebolavirus infections. Several Ebola virus (EBOV)-specific and, more recently, pan-ebolavirus antibody cocktails have been described. Here, we report the development and assessment of a Sudan virus (SUDV)-specific antibody cocktail. We produced a panel of SUDV glycoprotein (GP)-specific human chimeric monoclonal antibodies (mAbs) using both plant and mammalian expression systems and completed head-to-head in vitro and in vivo evaluations. Neutralizing activity, competitive binding groups, and epitope specificity of SUDV mAbs were defined before assessing protective efficacy of individual mAbs using a mouse model of SUDV infection. Of the mAbs tested, GP base-binding mAbs were more potent neutralizers and more protective than glycan cap- or mucin-like domain-binding mAbs. No significant difference was observed between plant and mammalian mAbs in any of our in vitro or in vivo evaluations. Based on in vitro and rodent testing, a combination of two SUDV-specific mAbs, one base binding (16F6) and one glycan cap binding (X10H2), was down-selected for assessment in a macaque model of SUDV infection. This cocktail, RIID F6-H2, provided protection from SUDV infection in rhesus macaques when administered at 50 mg/kg on days 4 and 6 postinfection. RIID F6-H2 is an effective postexposure SUDV therapy and provides a potential treatment option for managing human SUDV infection.

Patient safety education in pre-registration nursing programmes in South Korea.

AIMS: This study investigated how patient safety is currently taught in pre-registration nursing programmes across South Korea and explored nurse educators' perspectives on curriculum change. BACKGROUND: Pre-graduate education plays a critical role in preparing nurses with the requisite patient safety competencies. However, little is known about how patient safety education is addressed in South Korean nursing schools or the perspectives of nurse educators regarding patient safety education and a need for change. METHODS: This descriptive study used data collected during a 2019 accreditation workshop provided by the Korean Accreditation Board of Nursing Education. A paper-and-pencil survey was completed by 80 nurse educators working in 16 regions throughout Korea. RESULTS: A little consistency was found in approaches to teaching patient safety. Patient safety topics are addressed throughout various nursing courses, and patient safety education is limited in hours of instruction and breadth of content. A majority of respondents indicated that additional supports are needed, including a national standardized curriculum for patient safety education. CONCLUSION: A new approach to teaching patient safety is needed in Korean pre-registration nursing education. Overall, patient safety education is limited and provided through a fragmented approach with little attention to systems, workplace design or human issues that are necessary for developing the critical reasoning and skills to support patient safety. IMPLICATIONS FOR NURSING POLICY: The accrediting and regulatory bodies in South Korea should work together to develop and implement explicit standards of patient safety education and patient safety competencies for nursing students. Development of a standardized national curriculum is essential for providing a consistent, systematic and comprehensive approach to patient safety education in nursing programmes.

Protective mAbs and Cross-Reactive mAbs Raised by Immunization with Engineered Marburg Virus GPs.

The filoviruses, which include the marburg- and ebolaviruses, have caused multiple outbreaks among humans this decade. Antibodies against the filovirus surface glycoprotein (GP) have been shown to provide life-saving therapy in nonhuman primates, but such antibodies are generally virus-specific. Many monoclonal antibodies (mAbs) have been described against Ebola virus. In contrast, relatively few have been described against Marburg virus. Here we present ten mAbs elicited by immunization of mice using recombinant mucin-deleted GPs from different Marburg virus (MARV) strains. Surprisingly, two of the mAbs raised against MARV GP also cross-react with the mucin-deleted GP cores of all tested ebolaviruses (Ebola, Sudan, Bundibugyo, Reston), but these epitopes are masked differently by the mucin-like domains themselves. The most efficacious mAbs in this panel were found to recognize a novel "wing" feature on the GP2 subunit that is unique to Marburg and does not exist in Ebola. Two of these anti-wing antibodies confer 90 and 100% protection, respectively, one hour post-exposure in mice challenged with MARV.

Phylodynamics of foot-and-mouth disease virus O/PanAsia in Vietnam 2010-2014.

Foot-and-mouth disease virus (FMDV) is endemic in Vietnam, a country that plays an important role in livestock trade within Southeast Asia. The large populations of FMDV-susceptible species in Vietnam are important components of food production and of the national livelihood. In this study, we investigated the phylogeny of FMDV O/PanAsia in Vietnam, reconstructing the virus' ancestral host species (pig, cattle or buffalo), clinical stage (subclinical carrier or clinically affected) and geographical location. Phylogenetic divergence time estimation and character state reconstruction analyses suggest that movement of viruses between species differ. While inferred transmissions from cattle to buffalo and pigs and from pigs to cattle are well supported, transmission from buffalo to other species, and from pigs to buffalo may be less frequent. Geographical movements of FMDV O/PanAsia virus appears to occur in all directions within the country, with the South Central Coast and the Northeast regions playing a more important role in FMDV O/PanAsia spread. Genetic selection of variants with changes at specific sites within FMDV VP1 coding region was different depending on host groups analyzed. The overall ratio of non-synonymous to synonymous nucleotide changes was greater in pigs compared to cattle and buffalo, whereas a higher number of individual amino acid sites under positive selection were detected in persistently infected, subclinical animals compared to viruses collected from clinically diseased animals. These results provide novel insights to understand FMDV evolution and its association with viral spread within endemic countries. These findings may support animal health organizations in their endeavor to design animal disease control strategies in response to outbreaks.

Influence of a triclosan toothpaste on periodontopathic bacteria and periodontitis progression in cardiovascular patients: a randomized controlled trial.

BACKGROUND AND OBJECTIVE: Triclosan/copolymer toothpaste is effective in controlling plaque and gingivitis and in slowing the progression of periodontitis. This study describes its influence on microbiological and clinical outcomes, over a 5-year period, in patients with established cardiovascular disease (CVD). MATERIAL AND METHODS: Four-hundred and thirty-eight patients were recruited from the Cardiovascular Unit at The Prince Charles Hospital, Brisbane, Australia, and randomized to triclosan or placebo groups. Six sites per tooth were examined annually for probing pocket depth and loss of attachment. These outcomes were analysed, using generalized linear modelling, in 381 patients who had measurements from consecutive examinations. Concurrent load of the periodontal pathogens Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, Tannerella forsythia and Porphyromonas gingivalis was determined, using quantitative real-time PCR, in 437 patients with baseline plaque samples. Group comparisons were expressed as geometric means. The chi-square test was used to test for differences between the two groups of patients with regard to the proportion of patients with different numbers of bacterial species. RESULTS: There was no difference in general health or periodontal status between the groups at baseline. There was a significant reduction in the number of interproximal sites showing loss of attachment between examinations, by 21% on average (p < 0.01), in the triclosan group compared with the placebo group. The prevalence of patients with F. nucleatum and A. actinomycetemcomitans was high and remained relatively constant throughout the 5 years of the study. In contrast, the prevalence of T. forsythia and P. gingivalis showed more variability; however, there was no significant difference between the groups, at any time point, in the prevalence of any organism. A significant difference in the geometric means for P. gingivalis (p = 0.01) was seen at years 1 and 4, and for F. nucleatum (p = 0.01) and in the total bacterial load (p = 0.03) at year 2; however, these differences were not statistically significant following a Bonferroni correction for multiple comparisons. There was no difference between the groups in the geometric means for each organism at year 5. CONCLUSION: Within the limitations of the study, these data suggest that the use of triclosan/copolymer toothpaste significantly slowed the progression of periodontitis in patients with CVD but that it had little influence on key subgingival periodontopathic bacteria in these patients over the 5 years of the study.

Provider Perspectives on Promoting Cervical Cancer Screening Among Refugee Women.

Many refugees in the United States emigrated from countries where the incidence of cervical cancer is high. Refugee women are unlikely to have been screened for cervical cancer prior to resettlement in the U.S. National organizations recommend cervical cancer screening for refugee women soon after resettlement. We sought to identify health and social service providers' perspectives on promoting cervical cancer screening in order to inform the development of effective programs to increase screening among recently resettled refugees. This study consisted of 21 in-depth key informant interviews with staff from voluntary refugee resettlement agencies, community based organizations, and healthcare clinics serving refugees in King County, Washington. Interview transcripts were analyzed to identify themes. We identified the following themes: (1) refugee women are unfamiliar with preventive care and cancer screening; (2) providers have concerns about the timing of cervical cancer education and screening; (3) linguistic and cultural barriers impact screening uptake; (4) provider factors and clinic systems facilitate promotion of screening; and (5) strategies for educating refugee women about screening. Our findings suggest that refugee women are in need of health education on cervical cancer screening during early resettlement. Frequent messaging about screening could help ensure that women receive screening within the early resettlement period. Health education videos may be effective for providing simple, low literacy messages in women's native languages. Appointments with female clinicians and interpreters, as well as clinic systems that remind clinicians to offer screening at each appointment could increase screening among refugee women.

Role of serial EUS-guided FNA on pancreatic cystic neoplasms: a retrospective analysis of repeat carcinoembryonic antigen measurements.

BACKGROUND AND AIMS: Pancreatic cystic neoplasms (PCNs) often need interval surveillance, including repeat EUS, but the role of repeat FNA with fluid analysis is poorly defined. The aim of this analysis is to evaluate the potential clinical significance of serial carcinoembryonic antigen (CEA) measurements by EUS-guided FNA (EUS-FNA) in the surveillance for PCNs. PATIENTS: Patients who underwent EUS-FNA for PCNs were studied retrospectively. EUS-FNA findings were compared between index and prior procedures among patients who underwent repeat EUS-FNA. RESULTS: A total of 400 patients with PCNs underwent EUS-FNA. Eighty-seven of those patients had prior EUS-FNA with cyst fluid analysis. Patients with repeat FNA were significantly more likely to have multiple cysts (57% vs 41%; P = .008), multilocular cysts (75% vs 62%; P = .042), connection to pancreatic duct (33% vs 18%; P = .005), and higher initial CEA levels (94.8 vs 25.6 ng/mL; P = .003) compared with patients who had only a single FNA. A comparison of prior and index FNAs did not show significant differences in EUS or cyst fluid analysis findings. After log transformation, the association between CEA level at prior and index FNA was moderate (R2 = 0.626; P < .001), but cystic fluid CEA classification with a cutoff value of 192 ng/mL changed in 17 patients (20%), without significant changes in EUS findings. CONCLUSIONS: Repeat surveillance EUS-FNA resulted in stable CEA levels in the majority of patients, with spurious fluctuations of CEA in approximately 20% of patients. These data call into question any clinical significance attributed to an isolated interval rise in CEA level, especially in light of a stable EUS examination.

Screening of pigmented Bacillus aquimaris SH6 from the intestinal tracts of shrimp to develop a novel feed supplement for shrimp.

AIMS: To develop a novel feed supplement for shrimp using pigmented spore-forming bacterial strains isolated from their gastrointestinal tracts. METHODS AND RESULTS: Eight pigmented Bacillus strains were selected from the isolates based on high production of heat-stable spores, typical UV-Vis spectra of produced carotenoids (400-550 nm), and free radical scavenging activity of their extracts. Of the eight strains, the red-orange pigmented Bacillus aquimaris SH6 was selected because it showed the highest abundance in shrimp guts (70% population). Whiteleg shrimp (n = 30 per group) fed with SH6 spores, at >3 × 106  CFU g-1  pellet for 4 weeks had redder colour (score of 21-23 vs 20-22), 2·7-fold higher astaxanthin level (0·69 vs 0·25 µg g-1 shrimp), 34% higher weight gain (7·18 vs 5·32 g shrimp-1 ), and 85% higher phenoloxidase activity (OD490  = 0·265 vs 0·143) than shrimp in the control group. CONCLUSIONS: The result supports the potential use of B. aquimaris SH6 as a feed supplement for promoting the colourization and weight gain, and for enhancing innate immunity of whiteleg shrimp. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrates that carotenoids produced by B. aquimaris SH6 can be successfully absorbed and converted to astaxanthin in whiteleg shrimp.

Step-down vs. step-up noxious stimulation: differential effects on pain perception and patterns of brain activation.

BACKGROUND: We hypothesize that pain and brain responses are affected by changes in the presentation sequence of noxious stimuli that are, overall, identical in intensity and duration. METHODS: During functional magnetic resonance imaging (fMRI) scanning, 21 participants experienced three patterns of noxious stimulation: Up-type (step-up noxious stimulation, 15 s), Down-type (step-down noxious stimulation, 15 s), and Down-up-type (decreasing and increasing pattern of noxious stimulation, 15 s). The total intensity and duration of the three noxious stimulation patterns were identical, but the stimulation sequences were different. RESULTS: Pain and unpleasantness ratings in the Down- and Down-up-type noxious stimulations were lower than in the Up-type noxious stimulation. The left prefrontal cortex [(PFC, BA (Brodmann area) 10, (-45, 50, 1)] was more highly activated in the Down- and Down-up-type noxious stimulations than in the Up-type noxious stimulation. The S1, S2, insula, bilateral PFC (BA 46), and midcingulate cortex were more highly activated in the Up-type noxious stimulation than in the Down-type noxious stimulation. PFC BA 10 was located at an inferior level compared to the bilateral PFC BA 46 (Z axis = 1 for BA 10, compared to 22 and 25 for the right and left BA 46, respectively). When cortisol level was increased, the left hippocampal cortex, along with the left parahippocampal cortex, was greatly activated for the Up-type noxious stimulation. CONCLUSION: When pain cannot be avoided in clinical practice, noxious stimuli should be applied to patients in a step-down pattern that delivers the most intense pain first and the least intense pain last.

Mutational profiling of familial male breast cancers reveals similarities with luminal A female breast cancer with rare TP53 mutations.

BACKGROUND: Male breast cancer (MBC) is still poorly understood with a large proportion arising in families with a history of breast cancer. Genomic studies have focused on germline determinants of MBC risk, with minimal knowledge of somatic changes in these cancers. METHODS: Using a TruSeq amplicon cancer panel, this study evaluated 48 familial MBCs (3 BRCA1 germline mutant, 17 BRCA2 germline mutant and 28 BRCAX) for hotspot somatic mutations and copy number changes in 48 common cancer genes. RESULTS: Twelve missense mutations included nine PIK3CA mutations (seven in BRCAX patients), two TP53 mutations (both in BRCA2 patients) and one PTEN mutation. Common gains were seen in GNAS (34.1%) and losses were seen in GNAQ (36.4%), ABL1 (47.7%) and ATM (34.1%). Gains of HRAS (37.5% vs 3%, P=0.006), STK11 (25.0% vs 0%, P=0.01) and SMARCB1 (18.8% vs 0%, P=0.04) and the loss of RB1 (43.8% vs 13%, P=0.03) were specific to BRCA2 tumours. CONCLUSIONS: This study is the first to perform high-throughput somatic sequencing on familial MBCs. Overall, PIK3CA mutations are most commonly seen, with fewer TP53 and PTEN mutations, similar to the profile seen in luminal A female breast cancers. Differences in mutation profiles and patterns of gene gains/losses are seen between BRCA2 (associated with TP53/PTEN mutations, loss of RB1 and gain of HRAS, STK11 and SMARCB1) and BRCAX (associated with PIK3CA mutations) tumours, suggesting that BRCA2 and BRCAX MBCs may be distinct and arise from different tumour pathways. This has implications on potential therapies, depending on the BRCA status of MBC patients.

A comprehensive ovine model of blood transfusion.

BACKGROUND: The growing awareness of transfusion-associated morbidity and mortality necessitates investigations into the underlying mechanisms. Small animals have been the dominant transfusion model but have associated limitations. This study aimed to develop a comprehensive large animal (ovine) model of transfusion encompassing: blood collection, processing and storage, compatibility testing right through to post-transfusion outcomes. MATERIALS AND METHODS: Two units of blood were collected from each of 12 adult male Merino sheep and processed into 24 ovine-packed red blood cell (PRBC) units. Baseline haematological parameters of ovine blood and PRBC cells were analysed. Biochemical changes in ovine PRBCs were characterized during the 42-day storage period. Immunological compatibility of the blood was confirmed with sera from potential recipient sheep, using a saline and albumin agglutination cross-match. Following confirmation of compatibility, each recipient sheep (n = 12) was transfused with two units of ovine PRBC. RESULTS: Procedures for collecting, processing, cross-matching and transfusing ovine blood were established. Although ovine red blood cells are smaller and higher in number, their mean cell haemoglobin concentration is similar to human red blood cells. Ovine PRBC showed improved storage properties in saline-adenine-glucose-mannitol (SAG-M) compared with previous human PRBC studies. Seventy-six compatibility tests were performed and 17·1% were incompatible. Only cross-match compatible ovine PRBC were transfused and no adverse reactions were observed. CONCLUSION: These findings demonstrate the utility of the ovine model for future blood transfusion studies and highlight the importance of compatibility testing in animal models involving homologous transfusions.

Is paediatric trauma severity overestimated at triage? An observational follow-up study.

BACKGROUND: Severe paediatric trauma is rare, and pre-hospital and local hospital personnel experience with injured children is often limited. We hypothesised that a higher proportion of paediatric trauma victims were taken to the regional trauma centre (TC). METHODS: This is an observational follow-up study that involves one level I TC and seven local hospitals. We included paediatric (< 16 years) and adult (≥ 16-≤ 79 years) trauma patients with a driving distance to the TC > 30 minutes. The primary end-point was the proportion of trauma patients arriving in the TC. RESULTS: We included 1934 trauma patients, 238 children and 1696 adults. A total of 33/238 children (13.9%) vs. 304/1696 adults (17.9%) were transported to the TC post-injury (P = 0.14). Among these, children were significantly less injured than adults [median Injury Severity Score (ISS) 9 vs. 14, P < 0.01]. There was no significant difference between the groups in the proportion of seriously injured trauma victims (ISS > 15) taken to the TC [8/11 (72.7%) vs. 139/182 (76.4%)]. The corresponding figures for ISS < 15 were 25/227 (11.0%) and 164/1509 (10.9%), respectively. No significant difference was found in intensive care unit length of stay or time to TC arrival. No paediatric vs. 36/1671 (2.2%) adult deaths were observed at 30-day follow-up (P = 0.03). CONCLUSIONS: There was no difference in the proportion of paediatric and adult trauma patients transported to the TC, neither overall nor among severely injured patients. Paediatric trauma patients admitted to the TC were, however, significantly less injured than adults.

Understanding HPV vaccine uptake among Cambodian American girls.

Cervical cancer incidence rates vary substantially among racial/ethnic groups in the United States (US) with women of Southeast Asian descent having the highest rates. Up to 70 % of cervical cancers could be prevented by widespread use of the human papillomavirus (HPV) vaccine. However, there is a lack of information about HPV vaccine uptake among Southeast Asian girls in the US. We conducted a telephone survey of Cambodian women with daughters who were age-eligible for HPV vaccination. Survey items addressed HPV vaccination barriers, facilitators and uptake. Our study group included 86 Cambodian mothers who lived in the Seattle metropolitan area. The proportions of survey participants who reported their daughter had initiated and completed the HPV vaccine series were only 29 and 14 %, respectively. Higher levels of vaccine uptake were significantly associated with mothers having heard about the HPV vaccine from a health professional and having received a recent Pap test. Commonly cited barriers to HPV vaccination included lack of knowledge about the HPV vaccine, not having received a physician recommendation for HPV vaccination and thinking the HPV vaccine is unnecessary in the absence of health problems. Linguistically and culturally appropriate HPV educational programs should be developed and implemented in Cambodian American communities. These programs should aim to enhance understanding of disease prevention measures, increase knowledge about the HPV vaccine and empower women to ask their daughter's doctors for HPV vaccination.

Harnessing historical data to derive reference limits - A comparison of e-norms to traditionally derived reference limits.

Objective: Nerve conduction studies (NCS) require valid reference limits for meaningful interpretation. We aimed to further develop the extrapolated norms (e-norms) method for obtaining NCS reference limits from historical laboratory datasets for children and adults, and to validate it against traditionally derived reference limits. Methods: We compared reference limits obtained by applying a further developed e-norms with reference limits from healthy controls for the age strata's 9-18, 20-44 and 45-60 years old. The control data consisted of 65 healthy children and 578 healthy adults, matched with 1294 and 5628 patients respectively. Five commonly investigated nerves were chosen: The tibial and peroneal motor nerves (amplitudes, conduction velocities, F-waves), and the sural, superficial peroneal and medial plantar sensory nerves (amplitudes, conduction velocities). The datasets were matched by hospital to ensure identical equipment and protocols. The e-norms method was adapted, and reference limit calculation using both ±2 SD (original method) and ±2.5 SD (to compensate for predicted underestimation of population SD by the e-norms method) was compared to control data using ±2 SD. Percentage agreement between e-norms and the traditional method was calculated. Results: On average, the e-norms method (mean ±2 SD) produced slightly stricter reference limits compared to the traditional method. Increasing the e-norms range to mean ±2.5 SD improved the results in children while slightly overcorrecting in the adult group. The average agreement between the two methods was 95 % (±2 SD) and 96 % (±2.5 SD). Conclusions: The e-norms method yielded slightly stricter reference limits overall than ones obtained through traditional methods; However, much of the difference can be attributed to a few outlying plots where the raters found it difficult to apply e-norms correctly. The two methods disagreed on classification of 4-5% of cases. Our e-norms software is suited to analyze large amounts of raw NCS data; it should further reduce bias and facilitate more accurate ratings. Significance: With small adaptations, the e-norms method adequately replicates traditionally derived reference limits, and is a viable method to produce reference limits from historical datasets.

Endoscopic Posterior Cervical Foraminotomy Under Lateral Decubitus Position with Local Anesthesia.

BACKGROUND: Endoscopic posterior cervical foraminotomy is gaining popularity among endoscopic spine surgeons for the treatment of radiculopathy caused by foraminal stenosis. METHODS: This study describes a technique using the lateral decubitus position for endoscopic posterior cervical foraminotomy under monitored anesthesia care and local anesthesia only. RESULTS: A total of 10 patients with contraindications to general anesthesia underwent the procedure, resulting in improvement in cervical radicular pain with no perioperative complications. CONCLUSIONS: The findings suggest that this approach is a viable alternative for patients at high risk of general anesthesia care, expanding the surgical options for the treatment of radiculopathy.

A comparison of computed tomography angiography and digital subtraction angiography for the diagnosis of penetrating cerebrovascular injury: a prospective multicenter study.

OBJECTIVE: In this research, the authors sought to characterize the incidence and extent of cerebrovascular lesions after penetrating brain injury in a civilian population and to compare the diagnostic value of head computed tomography angiography (CTA) and digital subtraction angiography (DSA) in their diagnosis. METHODS: This was a prospective multicenter cohort study of patients with penetrating brain injury due to any mechanism presenting at two academic medical centers over a 3-year period (May 2020 to May 2023). All patients underwent both CTA and DSA. The sensitivity and specificity of CTA was calculated, with DSA considered the gold standard. The number of DSA studies needed to identify a lesion requiring treatment that had not been identified on CTA was also calculated. RESULTS: A total of 73 patients were included in the study, 33 of whom had at least 1 penetrating cerebrovascular injury, for an incidence of 45.2%. The injuries included 13 pseudoaneurysms, 11 major arterial occlusions, 9 dural venous sinus occlusions, 8 dural arteriovenous fistulas, and 6 carotid cavernous fistulas. The sensitivity of CTA was 36.4%, and the specificity was 85.0%. Overall, 5.6 DSA studies were needed to identify a lesion requiring treatment that had not been identified with CTA. CONCLUSIONS: Cerebrovascular injury is common after penetrating brain injury, and CTA alone is insufficient to diagnosis these injuries. Patients with penetrating brain injuries should routinely undergo DSA.

Therapeutic administration of a cross-reactive mAb targeting the fusion glycoprotein of Nipah virus protects nonhuman primates.

No licensed vaccines or therapies exist for patients infected with Nipah virus (NiV), although an experimental human monoclonal antibody (mAb) cross-reactive to the NiV and Hendra virus (HeV) G glycoprotein, m102.4, has been tested in a phase 1 trial and has been provided under compassionate use for both HeV and NiV exposures. NiV is a highly pathogenic zoonotic paramyxovirus causing regular outbreaks in humans and animals in South and Southeast Asia. The mortality rate of NiV infection in humans ranges from 40% to more than 90%, making it a substantial public health concern. The NiV G glycoprotein mediates host cell attachment, and the F glycoprotein facilitates membrane fusion and infection. We hypothesized that a mAb against the prefusion conformation of the F glycoprotein may confer better protection than m102.4. To test this, two potent neutralizing mAbs against NiV F protein, hu1F5 and hu12B2, were compared in a hamster model. Hu1F5 provided superior protection to hu12B2 and was selected for comparison with m102.4 for the ability to protect African green monkeys (AGMs) from a stringent NiV challenge. AGMs were exposed intranasally to the Bangladesh strain of NiV and treated 5 days after exposure with either mAb (25 milligrams per kilogram). Whereas only one of six AGMs treated with m102.4 survived until the study end point, all six AGMs treated with hu1F5 were protected. Furthermore, a reduced 10 milligrams per kilogram dose of hu1F5 also provided complete protection against NiV challenge, supporting the upcoming clinical advancement of this mAb for postexposure prophylaxis and therapy.