bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification and Functional Analysis of Tomato MicroRNAs in the Biocontrol Bacterium Pseudomonas putida Induced Plant Resistance to Meloidogyne incognita
Authors: Yang Fan , Ding Ling , Zhao Dan , Fan Haiyan , Zhu Xiaofeng , Wang Yuanyuan , Liu Xiaoyu , Duan Yuxi , Chen Lijie
Published: June 2022

Root-knot nematodes (RKNs, Meloidogyne spp.) seriously damage tomato production worldwide, and biocontrol bacteria can induce tomato immunity to RKNs. Our previous studies have revealed that Pseudomonas putida strain Sneb821 can trigger tomato immunity against M. incognita and that several long noncoding RNAs and microRNAs (miRNAs) are involved in this process. However, the molecular functions of the miRNAs in tomato immune responses remain unclear. In this study, deep small RNA sequencing identified 78 differentially expressed miRNAs in tomato plants inoculated with Sneb821 and M. incognita relative to plants inoculated with M. incognita alone; 38 miRNAs were upregulated, and 40 miRNAs were downregulated. The expression levels of six known miRNAs and five novel miRNAs were validated using RT-qPCR assays. These included Sly-miR482d-3p, Sly-miR156e-5p, Sly-miR319a, novel_miR_116, novel_miR_121, and novel_miR_221, which were downregulated, and Sly-miR390a-3p, Sly-miR394-3p, Sly-miR396a-3p, novel_miR_215, and novel_miR_83, which were upregulated in plants treated with Sneb821 and M. incognita. In addition, Sly-miR482d was functionally characterized through gene silencing and overexpression of its target gene NBS-LRR ( Solyc05g009750.1) in tomato and by challenging the plants with M. incognita inoculation. The number of second-stage juveniles (J2) inside roots and induced galls were significantly decreased in both Sly-miR482d-silenced plants and Solyc05g009750.1 overexpressing plants, whereas the activity of superoxide dismutase, peroxidase, and hydrogen peroxide content were significantly increased. The results suggest that Sneb821 could inhibit Sly-miR482d expression and thus regulate tomato immune responses against M. incognita infestation. This study provides novel insights into the biocontrol bacteria-mediated tomato immunity to M. incognita that engages with plant miRNAs.
IL‐10 promotes endothelial progenitor cell infiltration and wound healing via STAT3
Authors: Short Walker D. , Steen Emily , Kaul Aditya , Wang Xinyi , Olutoye Oluyinka O. , Vangapandu Hima V. , Templeman Natalie , Blum Alexander J. , Moles Chad M. , Narmoneva Daria A. , Crombleholme Timothy M. , Butte Manish J. , Bollyky Paul L. , Keswani Sundeep G. , Balaji Swathi
Published: June 2022

Endothelial progenitor cells (EPCs) contribute to de novo angiogenesis, tissue regeneration, and remodeling. Interleukin 10 (IL‐10), an anti‐inflammatory cytokine that primarily signals via STAT3, has been shown to drive EPC recruitment to injured tissues. Our previous work demonstrated that overexpression of IL‐10 in dermal wounds promotes regenerative tissue repair via STAT3‐dependent regulation of fibroblast‐specific hyaluronan synthesis. However, IL‐10's role and specific mode of action on EPC recruitment, particularly in dermal wound healing and neovascularization in both normal and diabetic wounds, remain to be defined. Therefore, inducible skin‐specific STAT3 knockdown mice were studied to determine IL‐10's impact on EPCs, dermal wound neovascularization and healing, and whether it is STAT3‐dependent. We show that IL‐10 overexpression significantly elevated EPC counts in the granulating wound bed, which was associated with robust capillary lumen density and enhanced re‐epithelialization of both control and diabetic (db/db) wounds at day 7. We noted increased VEGF and high C‐X‐C motif chemokine 12 (CXCL12) levels in wounds and a favorable CXCL12 gradient at day 3 that may support EPC mobilization and infiltration from bone marrow to wounds, an effect that was abrogated in STAT3 knockdown wounds. These findings were supported in vitro. IL‐10 promoted VEGF and CXCL12 synthesis in primary murine dermal fibroblasts, with blunted VEGF expression upon blocking CXCL12 in the media by antibody binding. IL‐10‐conditioned fibroblast media also significantly promoted endothelial sprouting and network formation. In conclusion, these studies demonstrate that overexpression of IL‐10 in dermal wounds recruits EPCs and leads to increased vascular structures and faster re‐epithelialization.
Addressing comorbidities in the perioperative setting and optimizing perioperative medicine education
Authors: Krishnan Sindhu , Adeola Janet O. , Urman Richard D.
Published: June 2022

Purpose of review

Preoperative clinics and patient optimization are examples of collaborative, multidisciplinary care pathways that create value. This article reviews current literature to demonstrate the importance of preoperative enhancement of patients’ cognitive and functional status. This article underscores the importance of formal training in multidisciplinary topics, such as frailty, brain health, and shared decision-making for anesthesiology house staff.

Recent findings

Preoperative cognitive screening of older patients is a valuable metric for risk stratification and detection of patients at risk of postoperative delirium. Frailty is another syndrome that can be identified and optimized preoperatively. Sarcopenia has been shown to correlate with frailty; this shows promise as a method to detect frailty preoperatively.

Anesthesiologists as perioperative physicians are in a unique position to lead and coordinate interdisciplinary conversations that incorporate patient goal concordant care and realistic assessment of perioperative complications. Formal house staff training in early recognition and management of patients at risk of adverse outcomes in the short and long term postoperatively improves patient outcomes and decreases healthcare spending.
Perioperative considerations for adult patients with obstructive sleep apnea
Authors: Weingarten Toby N. , Sprung Juraj
Published: June 2022

Purpose of review

Obstructive sleep apnea (OSA) is a common, but often undiagnosed, sleep breathing disorder affecting approximately a third of adult surgical patients. OSA patients have increased sensitivity to anesthetic agents, sedatives, and opioid analgesics.

Recent findings

Newer technologies (e.g., bedside capnography) have demonstrated that OSA patients have repetitive apneic spells, beginning in the immediate postoperative period and peaking in frequency during the first postoperative night. Compared to patients without OSA, OSA patients have double the risk for postoperative pulmonary as well as other complications, and OSA has been linked to critical postoperative respiratory events leading to anoxic brain injury or death. Patients with OSA who have respiratory depression during anesthesia recovery have been found to be high-risk for subsequent pulmonary complications. Gabapentinoids have been linked to respiratory depression in these patients.

Surgical patients should be screened for OSA and patients with OSA should continue using positive airway pressure devices postoperatively. Use of shorter acting and less sedating agents and opioid sparing anesthetic techniques should be encouraged. In particular, OSA patients exhibiting signs of respiratory depression in postanesthesia recovery unit should receive enhancer respiratory monitoring following discharge to wards.
After nectarine: how should we provide anesthesia for neonates?
Authors: Bertolizio Gianluca , Disma Nicola , Engelhardt Thomas
Published: June 2022

Purpose of review

Neonates have a high risk of perioperative morbidity and mortality. The NEonate and Children audiT of Anaesthesia pRactice IN Europe (NECTARINE) investigated the anesthesia practice, complications and perioperative morbidity and mortality in neonates and infants <60 weeks post menstrual age requiring anesthesia across 165 European hospitals. The goal of this review is to highlight recent publications in the context of the NECTARINE findings and subsequent changes in clinical practice.

Recent findings

A perioperative triad of hypoxia, anemia, and hypotension is associated with an increased overall mortality at 30 days. Hypoxia is frequent at induction and during maintenance of anesthesia and is commonly addressed once oxygen saturation fall below 85%.

Blood transfusion practices vary widely variable among anesthesiologists and blood pressure is only a poor surrogate of tissue perfusion. Newer technologies, whereas acknowledging important limitations, may represent the currently best tools available to monitor tissue perfusion. Harmonization of pediatric anesthesia education and training, development of evidence-based practice guidelines, and provision of centralized care appear to be paramount as well as pediatric center referrals and international data collection networks.

The NECTARINE provided new insights into European neonatal anesthesia practice and subsequent morbidity and mortality.

Maintenance of physiological homeostasis, optimization of oxygen delivery by avoiding the triad of hypotension, hypoxia, and anemia are the main factors to reduce morbidity and mortality. Underlying and preexisting conditions such as prematurity, congenital abnormalities carry high risk of morbidity and mortality and require specialist care in pediatric referral centers.
Monitoring of analgesia level during general anesthesia in children
Authors: Sabourdin Nada , Constant Isabelle
Published: June 2022

Purpose of review

Monitoring of intraoperative nociception has made substantial progress in adult anesthesia during the last 10 years. Several monitors have been validated and their use has been associated with intraoperative or postoperative benefits in the adult population. In pediatric anesthesia, less data are available. However, several recent publications have assessed the performance of nociception monitors in children, and investigated their potential benefits in this context. This review will describe the main validated intraoperative nociception monitors, summarize adult findings and describe the available pediatric data.

Recent findings

Six intraoperative nociception indices were included in this review. Among them, four have shown promising results in children: Surgical Pleth Index (GE-Healthcare, Helsinki, Finland), Analgesia-Nociception Index (Mdoloris Medical Systems, Loos, France), Newborn-Infant Parasympathetic Evaluation (Mdoloris Medical Systems), and Pupillometry (IDMED, Marseille, France). The relevance of Skin Conductance (MedStorm innovations, AS, Oslo, Norway) under general anesthesia could not be established. Finally, the Nociception Level (Medasense, Ramat Gan, Israel) still requires to be investigated in children.

To date, four monitors may provide a relevant assessment of intraoperative nociception in children. However, the potential clinical benefits associated with their use to guide analgesia remain to be demonstrated.
Workforce solutions to address health disparities
Authors: Mhyre Jill M. , Jackson Jaleesa , Lucero Jennifer , Goree Johnathan
Published: June 2022

Purpose of review

This review focuses on physician workforce racial & ethnic diversity as a solution to improve perioperative and peripartum health equity.

Recent findings

Black, Indigenous, and Hispanic physicians remain underrepresented in medicine (URiM) and anesthesiology, and efforts to expand this workforce have had limited impact. Psychological forces, including implicit bias, aversive racism, outgroup bias, racial attention bias, stereotype threat, and imposter syndrome all act to reinforce structural racism and decrease opportunity for advancement. Evidence based solutions are emerging, but require institutional commitment and widespread engagement of the entire medical community.

Academic medicine has recognized the need to diversify the physician workforce for more than 50 years, and yet Black, Indigenous, and Hispanic physicians remain URiM. Foundational assumptions and power structures in medicine limit entry, advancement, and retention of URiM physicians. Solutions require leadership and institutional commitment to change the policies, procedures, priorities, and culture of academic medicine.
Double-level Intraperiosteal Derotational Osteotomy for Congenital Radioulnar Synostosis
Authors: Martínez-Álvarez Sergio , González-Codó Sergio , Vara-Patudo Isabel , Galán-Olleros María , Fraga-Collarte Manuel , Palazón-Quevedo Ángel
Published: June 2022

Background:

Many operative methods have been reported for the treatment of congenital radioulnar synostosis (CRUS) and their indications remain controversial. The aim of this study is to evaluate the clinical, radiologic, and functional results of the 2-stage derotational osteotomy with periosteal preservation for CRUS in children.

Methods:

From a total of 102 children with CRUS, a retrospective evaluation of 14 consecutive patients (18 forearms) who underwent 2-stage derotational osteotomy of the distal third radius and proximal third ulna with periosteal preservation, bone segment removal, morselization and grafting and cast immobilization was performed. Children with bilateral involvement and/or pronation (>60 degrees), and substantial functional limitations in daily activities were considered candidates for surgery to obtain the desired position of 0 to 20 degrees of pronation. Electronic medical records, preoperative and postoperative clinical and radiologic examinations were reviewed. Also, functional results and parental satisfaction were assessed and statistically analyzed.

Results:

The median age at the time of surgery was 6.87 (5.02 to 11.22) years. The median follow-up was 38.62 (24.79 to 81.20) months. The median preoperative pronation deformity was 80 (70 to 90) degrees, while the final position was 0 (0 to 10) degrees of pronation (P<0.01). Elbow flexion and extension showed no changes after surgery. All patients successfully achieved union at 8 (6 to 10) weeks. No complications were observed, and no patient required revision surgeries. The ability to perform daily activities improved markedly, and all patients were satisfied with the results of the surgery.

Conclusions:

Two-stage double-level intraperiosteal derotational osteotomy is a safe, simple, and effective procedure in children with CRUS with severe deformity and limitation in performing basic daily living activities. Functional improvement and patient satisfaction are total, and so far no complications have been reported.

Level of Evidence:

Level III—treatment study, retrospective comparative study.
Screw Thread Configuration Has No Effect on Outcomes of In Situ Fixation for Stable Slipped Capital Femoral Epiphysis
Authors: Via Garrhett G. , Brueggeman David A. , Lyons Joseph G. , Edukugho Derrek O. , Froehle Andrew W. , Martinek Melissa A. , Albert Michael C.
Published: June 2022

Background:

No consensus exists regarding the optimal surgical management of slipped capital femoral epiphysis (SCFE). Treatment goals include avoiding slip progression and sequelae such as avascular necrosis (AVN). Factors associated with surgical implants merit further research. This study investigates the effect of screw thread configuration and the number of screws on surgical outcomes.

Methods:

A total of 152 patients undergoing cannulated, stainless steel, in situ screw fixation of SCFE between January 2005 and April 2018 were included. Procedure laterality, screw number and thread configuration (partially threaded/fully threaded), bilateral diagnosis, Loder classification, final follow-up, patient demographics, and endocrinopathy history were analyzed. Primary outcomes were return to the operating room (ROR), AVN, hardware failure/removal, and femoroacetabular impingement (FAI).

Results:

Most patients received a single (86.2%), partially threaded (81.6%) screw; most were unilateral (67.8%) and stable (79.6%). Mean follow-up was 2.0±2.7 years, with a 15.8% rate of ROR, 5.3% exhibiting AVN, 6.6% exhibiting FAI, and 9.2% experiencing hardware failure/removal. Number of screws was the sole predictor of ROR [odds ratio (OR)=3.35, 95% confidence interval (CI): 1.18-9.49]. Unstable SCFE increased the odds of AVN (OR=38.44; 95% CI: 4.35-339.50) as did older age (OR=1.43, 95% CI: 1.01-2.03). Female sex increased risk for FAI (OR=4.87, 95% CI: 1.20-19.70), and bilateral SCFE elevated risk for hardware failure/removal versus unilateral SCFE (OR=4.41, 95% CI: 1.39-14.00). Screw thread configuration had no significant effect on any outcome (for each, P≥0.159).

Conclusions:

Rates of ROR, AVN, FAI, and hardware failure/removal did not differ between patients treated with partially threaded or fully threaded screws. The use of 2 screws was associated with an increased likelihood of ROR. These findings suggest that screw thread configuration has no impact on complication rates, whereas screw number may be an important consideration in SCFE fixation.

Level of Evidence:

Level III—retrospective cohort study.
Recent advances in the treatment of advanced prostate cancer: maximizing existing therapies while searching for novel solutions
Authors: Gourdin Theodore
Published: June 2022

Purpose of review

Present highlights from recent research examining treatment of advanced prostate cancer.

Recent findings

Data are emerging that combining androgen deprivation, docetaxel, and additional androgen-receptor-targeted therapies in treatment naïve metastatic prostate cancer may be an effective strategy to improve outcomes. Genomically targeted therapies and radiopharmaceuticals continue to be evaluated in the treatment of advanced castration-resistant prostate cancer.

Although no clear consensus has emerged regarding the best sequencing of available therapeutics, trial results continue to support moving available therapies earlier in the disease course. Data continue to build for novel radiopharmaceuticals soon to likely be approved for treatment of castration-resistant disease.
Utilization of Our Toolkit: A Systematic Review and Meta-analysis of Surgical Therapies in Vitiligo Treatment
Authors: McCrary Myles R. , Gibbs David C. , Alharthi Maher , Krueger Loren D.
Published: June 2022

BACKGROUND

Although vitiligo is often treated medically, there is increasing evidence for surgical therapies. Overlap with in-office surgical therapies that are already employed for other dermatologic conditions suggest that there is a significant opportunity to expand dermatologists' therapeutic repertoire for vitiligo.

OBJECTIVE

To systematically review the efficacy of nonphototherapy surgical treatments for vitiligo in comparative or placebo-controlled trials.

METHODS

A systematic review for surgical treatments for vitiligo was conducted. Primary outcomes were treatment success (>75% repigmentation) and failure (<25% repigmentation) for which meta-analyses were performed. Adverse effects were noted. The Cochrane risk of bias tool was used to assess study quality.

RESULTS

Surgical treatments reviewed included platelet-rich plasma, microneedling, ablative therapies, and surgical modalities. Seventy-three studies with 2,911 patients were included. The repigmentation benefits and adverse events are summarized. Meta-analyses suggest benefits for ablative laser therapies or microneedling in combination with narrowband ultraviolet B (NB-UVB) and for suction blister epidermal grafting over punch grafting.

CONCLUSION

The addition of microneedling or ablative laser therapy to NB-UVB phototherapy may improve repigmentation with minimal adverse effects. Surgical therapies, such as suction blister grafting and punch grafting, may offer the highest likelihood of repigmentation but have a risk of adverse effects including scarring and hyperpigmentation.
Medical Students’ Exposure to Plastic Surgery: A Cross-sectional Review of Scholarly and Academic Opportunities
Authors: Antezana Luis A. , Xie Katherine Z. , Weissler Jason M. , Bakri Karim
Published: June 2022

Background:

Specialty exposure is most influential in a medical student’s decision to pursue plastic surgery training. We aimed to understand what opportunities exist for students through national plastic surgery organizations.

Methods:

The American Board of Plastic Surgery, American Society of Plastic Surgeons, and The Aesthetic Society provide online lists of related organizations. Cross-referencing lists yielded 47 unique organizations. Screening for presence of annual meeting and relevance to student and resident education yielded 14 organizations. Bylaws/web-domains were reviewed for information related to the annual meeting, leadership opportunities, membership, grants, and travel scholarships. If available, previrtual/in-person and virtual meeting prices were collected. Lastly, discrepancies between webpage information and phone/email correspondence were noted.

Results:

All (100%) organizations welcomed students at annual meetings. Eleven promoted student presentation/submission. Average student registration fee was $109.3 ± SD$136.5 compared with $181.20 ± SD$157.20 for residents. Of organizations providing previrtual and virtual pricing (n = 10, 71.4%), there was an average price reduction in student registration of $92 (range: $0–375). Average student membership was $31.70/year ± SD $45.50 compared with $38.80 per year ± SD $65.90 for residents. The percentages of organizations offering student research grants, travel scholarships, and national student leadership were 21.4% (n = 3), 35.8% (n = 5), and 28.6% (n = 4) respectively. No organizations had student chapters/committees. All organizations (100%) contained at least one discrepancy between webpage/bylaw and email/phone.

Conclusions:

Our results suggest that although national opportunities seem to be limited, a role exists for further engagement, with interested students eager to take the initiative. Virtual conferences present a lower-cost alternative for students and residents.
Deploying Advanced Practice Practitioners in Response to the Healthcare Workforce Crisis in the Ambulatory Setting
Authors: Neagle Paul E.
Published: June 2022

The clinical staffing shortages that the US healthcare sector is experiencing are sure to become even more profound as the general population continues to grow and age. With more people living well beyond age 65, more physicians will be needed to provide care.

A solution to help fill the gaps in physician coverage is centered on the use of advanced practice practitioners, especially in the ambulatory setting. The growing shortage of primary care physicians could be significantly reduced or eliminated if the appropriate contributions of advanced practice practitioners—including physician assistants/physician associates (PAs) and nurse practitioners (NPs)—are considered when calculating financial costs.

My organization uses a model in the ambulatory setting that emphasizes the use of PAs and NPs who are supported by physician oversight in their clinical practice. Throughout the critical challenges of the recent past, the model has served us well. Other organizations may also see important benefits with this strategy.
Deep Anterior Lamellar Keratoplasty: Can All Ruptures Be Fixed?
Authors: Sarnicola Caterina , Sarnicola Enrica , Cheung Albert Y. , Sarnicola Vincenzo
Published: June 2022

Purpose:

The aim of this study was to report our experience in managing different types of Descemet membrane (DM) ruptures during deep anterior lamellar keratoplasty (DALK).

Methods:

This study was a retrospective, consecutive, interventional case series of 1573 DALK procedures conducted on 1244 patients, performed between 2002 and 2017. Inclusion criteria consisted of a minimum of 24-month follow-up. DM rupture incidence, location, and surgical approach for repair were recorded. Postoperative measures were investigated only in eyes that experienced DM ruptures and included best spectacle-corrected visual acuity, endothelial cell loss, double anterior chamber, pupillary block, need for rebubbling, graft clarity, and rejection episodes.

Results:

One thousand four hundred forty-three eyes met the inclusion criteria. DM ruptures occurred in 119 eyes (8.25%). Seventy-eight percent of DM ruptures were microruptures (≤2 mm), and they occurred more frequently during manual DALK cases. Macroruptures were less frequent (22%), and they occurred more frequently during subtotal and total anterior lamellar keratoplasty (STALK-TALK) cases. In general, DM ruptures mainly occurred in the peripheral cornea (95% of cases). One hundred (84%) of the 119 ruptures resolved by the first postoperative day. Nineteen cases (16%) developed double anterior chamber; all resolved by using different strategies. No intraoperative penetrating keratoplasty conversion was recorded. Pupillary block occurred in 7 cases (5.9%), but no Urrets-Zavalia syndrome was observed. The average postoperative endothelial cell loss was 410 ± 39 cells/mm2 (19%) at 1-year follow-up, and there was no significant difference between cases requiring a rebubbling and cases that did not (P = 0.896). All grafts but one were clear at the last follow-up. Graft failure from endothelial decompensation occurred in this lone case (0.8%).

Conclusions:

It is worth trying to repair all DM ruptures in DALK, and immediate penetrating keratoplasty conversion should be avoided. Understanding the physiomechanical mechanisms in DALK allows to correctly choose a proper rescue strategy to successfully repair DM ruptures.
Elevated Neuropeptides in Dry Eye Disease and Their Clinical Correlations
Authors: Yang Tingting , Zhou Yifan , Ma Baikai , Duan Hongyu , Liu Rongjun , Zhao Lu , Qi Hong
Published: June 2022

Purpose:

The goal of this study was to assess neuropeptide levels in patients with dry eye disease (DED) and investigate their correlations with clinical characteristics.

Methods:

This study included 38 eyes of 38 patients diagnosed with DED (DED group) and 38 eyes of 38 healthy volunteers without DED (control group). Ocular surface evaluation was performed. The severity of dry eye symptoms and signs in the DED group was graded. Neuropeptides [substance P (SP), alpha-melanocyte-stimulating hormone (α-MSH), β-endorphin, neurotensin, and oxytocin] and inflammatory cytokines levels were measured in basal tears. The link between neuropeptides and clinical parameters was investigated using Spearman rank correlation.

Results:

Overall, 76.3% of patients in the DED group showed dry eye symptoms and signs that were inconsistent in severity. Compared with the control group, the DED group showed higher levels of SP, α-MSH, and oxytocin in tears (P = 0.012, P = 0.030, and P = 0.006, respectively), but similar levels of β-endorphin and neurotensin (P = 0.269 and P = 0.052). The levels of SP, α-MSH, and oxytocin were elevated in DED patients with higher grading of symptoms than clinical signs (all P < 0.05). SP, α-MSH, and oxytocin levels in tears were positively correlated with Ocular Surface Disease Index scores, frequency of sensitivity to light, and frequency of blurred vision (all P < 0.05).

Conclusions:

The increased tear levels of SP, α-MSH, and oxytocin may be linked to ocular discomfort in DED. Neuropeptides may play a key role in the development of DED, especially in DED patients with more severe symptoms than clinical signs.
Improved Success Rate with Corticocancellous Block Compared to Cancellous-Only Trephine Technique in Alveolar Bone Grafting from the Iliac Crest
Authors: Lee James C. , Alford Jake , Willson Thomas , Ozaki Wayne
Published: June 2022

Background:

Alveolar bone grafting is an important component of cleft lip and palate treatment, with iliac crest as the most common donor site. Although studies have attempted to quantify alveolar bone graft resorption, few have directly compared the outcomes of graft techniques. This study compared the long-term success rates of corticocancellous block to trephine cancellous-only alveolar bone grafting from the iliac crest.

Methods:

A retrospective review of all cleft lip and palate patients undergoing alveolar bone grafting over 14 years was performed. Power analysis was performed to determine sample size. Data including patient demographics, surgical technique, need for repeated grafting, complications, length of hospitalization, and follow-up were collected. Statistical analyses of outcomes were performed based on initial graft technique.

Results:

A total of 106 initial operations met criteria, with 73 using trephine technique, 30 using corticocancellous block, and three undergoing open cancellous harvest. The overall regraft rate was 40 percent, with an average follow-up of 43.5 months. Patients with corticocancellous block grafting had significantly lower rates of repeated grafting compared to trephine technique (16.7 percent versus 47.9 percent; p < 0.001). There was no significant difference in complication rates or length of admission between treatment groups.

Conclusions:

The use of corticocancellous block alveolar bone grafting demonstrated significantly higher success rates when compared to cancellous-only trephine techniques, with no difference in complication rates. Although this must be weighed against the minor disadvantages of open iliac harvest, surgeons should consider incorporating en bloc corticocancellous bone to optimize outcomes in alveolar bone grafting.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Trends in the incidence rates of lower limb amputation due to nondiabetic peripheral artery disease in a large industrial city in Western Siberia, Russia: A review from 1996 to 2019
Authors: Vasilchenko Elena , Zoloev Georgy , Karapetian Karine , Puzin Sergey
Published: June 2022

Background:

lower limb amputation (LLA) is a growing problem in the population with and without diabetes mellitus. Monitoring the incidence rates of LLA is important for health care planning and has implications for the future problems of medical and social care.

Objective:

This study aimed to determine the trends in incidence rates of LLA due to nondiabetic peripheral artery disease in Novokuznetsk, Western Siberia, Russia.

Study design:

An observational study.

Methods:

Data on all transtibial and transfemoral amputations performed in inpatient facilities in Novokuznetsk from 1996 to 2019 were derived from the regional Register of patients with limb amputations. The rates were calculated per 100,000 population.

Results:

A total of 2448 persons with amputations due to nondiabetic peripheral artery disease were included in this study (3191 amputations). The overall incidence rate of LLA in Novokuznetsk increased from 14.6 in 1996 to 30.4 in 2019. The proportion of persons older than 60 years increased from 15.5% in 1996 to 20.3% in 2019.

Conclusion:

The expected aging of the population and increasing incidence of LLA are relevant issues in Russia. These findings can contribute to improving healthcare services and the development of prevention programs to reverse the alarming trend.
THE WNK4/SPAK PATHWAY STIMULATES ALVEOLAR FLUID CLEARANCE BY UPREGULATION OF EPITHELIAL SODIUM CHANNEL IN MICE WITH LIPOPOLYSACCHARIDE-INDUCED ACUTE RESPIRATORY DISTRESS SYNDROME
Authors: Deng Wang , Qi Di , Tang Xu-Mao , Deng Xin-Yu , He Jing , Wang Dao-Xin
Published: June 2022

With-No lysine Kinases (WNKs) have been newly implicated in alveolar fluid clearance (AFC). Epithelial sodium channels (ENaCs) serve a vital role in AFC. The potential protective effect of WNK4 in acute respiratory distress syndrome (ARDS), mediated by ENaC-associated AFC was investigated in the study. A model of lipopolysaccharide (LPS)-induced ARDS was established in C57BL/6 mice. WNK4, Sterile 20-related proline-alanine-rich kinase (SPAK), small interfering RNA (siRNA)-WNK4 or siRNA-SPAK were transfected into mouse lung or primary alveolar epithelial type II (ATII) cells. AFC, bronchoalveolar lavage fluid and lung histomorphology were determined. The expression of ENaC was determined to investigate the regulation of AFC by WNK4-SPAK signaling pathway. Activation of WNK4-SPAK signaling improved lung injury and survival rate, with enhanced AFC and reduced pulmonary edema via the upregulation of ENaC in ARDS. In primary rat ATII cells, gene-silencing by siRNA transfection reduced ENaC expression and the level of WNK4-associated SPAK phosphorylation. Immunoprecipitation revealed that the level of neural precursor cell-expressed developmentally downregulated gene 4 (Nedd4-2) binding to ENaC was decreased as a result of WNK4-SPAK signaling. The present study demonstrated that the WNK4/SPAK pathway improved AFC during LPS-induced ARDS, which is mainly dependent on the upregulation of ENaC with Nedd4-2-mediated ubiquitination.
Systematic HIV-1 promoter targeting with CRISPR/dCas9-VPR reveals optimal region for activation of the latent provirus
Authors: Klinnert Sarah , Chemnitzer Alex , Rusert Peter , Metzner Karin J.
Published: June 2022

CRISPR/dCas9-based activation systems (CRISPRa) enable sequence-specific gene activation and are therefore of particular interest for the ‘shock and kill’ cure approach against HIV-1 infections. This approach aims to activate the latent HIV-1 proviruses in infected cells and subsequently kill these cells. Several CRISPRa systems have been shown to specifically and effectively activate latent HIV-1 when targeted to the HIV-1 5′LTR promoter, making them a promising ‘shock’ strategy. Here, we aimed to evaluate the dCas9-VPR system for its applicability in reversing HIV-1 latency and identify the optimal gRNA target site in the HIV-1 5′LTR promoter leading to the strongest activation of the provirus with this system. We systematically screened the HIV-1 promoter by selecting 14 specific gRNAs that cover almost half of the HIV-1 promoter from the 3′ half of the U3 until the beginning of the R region. Screening in several latently HIV-1 infected cell lines showed that dCas9-VPR leads to a high activation of HIV-1 and that gRNA-V and -VII induce the strongest activation of replication competent latent provirus. This data indicates that the optimal activation region in the HIV-1 promoter for the dCas9-VPR system is located −165 to −106 bp from the transcription start site and that it is consistent with the optimal activation region reported for other CRISPRa systems. Our data demonstrates that the dCas9-VPR system is a powerful tool for HIV-1 activation and could be harnessed for the ‘shock and kill’ cure approach.
The impact of VITEK 2 implementation for identification and susceptibility testing of microbial isolates in a Brazilian public hospital
Authors: Decarli Ariadne , Nascimento Laís Vieira , Hiromi Sayama Esteves Larissa , Arenas Rocha Patrícia , Yuki Valéria Midori Gutoski , Cieslinski Juliette , Telles João Paulo , Ribeiro Victoria Stadler Tasca , Tuon Felipe Francisco
Published: June 2022

Introduction. The use of automated systems in identification and susceptibility tests can improve antimicrobial therapy, and positively impact clinical outcomes with a decrease in antimicrobial resistance, hospitalization time, costs, and mortality.

Aim. The aim of this study was to evaluate the clinical impact of an automated method for identification and susceptibility testing of microbial isolates.

Methodology. This was a retrospective cross-sectional study aimed to analyse the results before and after the implementation period of a VITEK 2 system in a Brazilian university hospital. Based on data from medical records, patients with a positive culture of clinical samples from January to July 2017 (conventional method) and from August to December 2017 (automated method) were included in this study. Demographic data, hospitalization time, time interval between culture collection and results, culture results and site, susceptibility profile, minimum inhibitory concentration, and outcome data were evaluated. Chi-square and Fischer’s tests were used in the analysis.

Results. Of the total samples, 836 were considered valid by the inclusion criteria, with 219 patients before VITEK 2 system implementation group and 545 in the post-implementation group. The comparison between the two periods showed a reduction of 25 % of the time to culture reports, a decrease of 33.5 to 17.0 days of hospitalization, and a reduction in mortality from 44.3–31.0 %, respectively.

Conclusion. The VITEK 2 system provided early access to appropriate antimicrobial therapy for patients and effected a positive clinical impact with a reduction in mortality and hospitalization time.
Lactobacilli and human dental caries: more than mechanical retention
Authors: Wen Zezhang T. , Huang Xiaochang , Ellepola Kassapa , Liao Sumei , Li Yihong
Published: June 2022

Lactobacilli have been considered as major contributors to human dental caries for over a century. Recent in vitro model studies have shown that when compared to Streptococcus mutans, a keystone pathogen of human dental caries, the ability of lactobacilli to form biofilms is poor, although differences exist between the different major species. Further studies using molecular and bioinformatics approaches provide evidence that multiple mechanisms, including adhesin-receptor mediated physical contact with

S. mutans

, facilitate the adherence and establishment of lactobacilli on the tooth surface. There is also evidence that under conditions like continuous sugar consumption, weak acids and other antimicrobials such as bacteriocins from lactobacilli can become detrimental to the microbial community, especially those in the proximity. Details on the underlying mechanisms of how different

Lactobacillus

sp. establish and persist in the highly complex microbiota on the tooth surface await further investigation.
Evolutionarily conserved midbody reorganization precedes ring canal formation during gametogenesis
Authors: Price Kari L. , Tharakan Dyuthi M. , Cooley Lynn
Published: June 2022

How canonical cytokinesis is altered during germ cell division to produce stable intercellular bridges called ring canals is poorly under-stood. Here, using time-lapse imaging in Drosophila, we observe that ring canal formation occurs via reorganization of the germline mid-body, a structure classically associated with its function in recruiting abscission-regulating proteins in complete cytokinesis. Germline midbodies reorganize from a focus into a ring rather than being discarded, and this transition is accompanied by changes in centralspindlin dynamics. The midbody-to-ring canal transformation is conserved in the Drosophila male and female germlines and during mouse and Hydra spermatogenesis. In Drosophila, ring canal formation depends on Citron kinase function in stark contrast to its role in abscission during somatic cell cytokinesis. Our results challenge existing models of ring canal formation, and provide important insights into broader functions of incomplete cytokinesis events across biological systems, such as those observed during development and disease states.
Longitudinal assessment of brain structure and behavior in youth with rapid weight gain: Potential contributing causes and consequences
Authors: Adise Shana , Marshall Andrew T. , Hahn Sage , Zhao Shaomin , Kan Eric , Rhee Kyung E. , Herting Megan M. , Sowell Elizabeth R.
Published: June 2022

Objective

Independent of weight status, rapid weight gain has been associated with underlying brain structure variation in regions associated with food intake and impulsivity among pre-adolescents. Yet, we lack clarity on how developmental maturation coincides with rapid weight gain and weight stability.

Methods

We identified brain predictors of two-year rapid weight gain and its longitudinal effects on brain structure and impulsivity in the Adolescent Brain Cognitive DevelopmentSM Study®. Youth were categorized as Healthy Weight/Weight Stable (WSHW, n=225) or Weight Gainers (WG, n=221, >38lbs); 63% of the WG group were healthy weight at 9-to-10-years-old.

Results

A five-fold cross-validated logistic elastic-net regression revealed that rapid weight gain was associated with structural variation amongst 39 brain features at 9-to-10-years-old in regions involved with executive functioning, appetitive control, and reward sensitivity. Two years later, WG youth showed differences in change over time in several of these regions and performed worse on measures of impulsivity.

Conclusions

These findings suggest that brain structure in pre-adolescence may predispose some to rapid weight gain and that weight gain itself may alter maturational brain change in regions important for food intake and impulsivity. Behavioral interventions that target inhibitory control may improve trajectories of brain maturation and facilitate healthier behaviors.
Automated real-time EEG sleep spindle detection for brain state-dependent brain stimulation
Authors: Hassan Umair , Feld Gordon , Bergmann Til Ole
Published: June 2022

Sleep spindles are a hallmark electroencephalographic (EEG) feature of non-rapid eye movement (NREM) sleep and believed to be instrumental for sleep-dependent memory reactivation and consolidation. However, direct proof of their causal relevance is hard to obtain, and our understanding of their immediate neurophysiological consequences is limited. To investigate their causal role, spindles need to be targeted in real-time with sensory or non-invasive brain stimulation techniques. While fully automated offline detection algorithms are well established, spindle detection in real time is highly challenging due to their spontaneous and transient nature. Here, we present the real-time spindle detector (RTSD), a robust multi-channel EEG signal processing algorithm that enables the automated triggering of stimulation during sleep spindles in a phase-specific manner. We validated the RTSD method by streaming pre-recorded sleep EEG datasets to a real-time computer system running a Simulink® Real-Time™ implementation of the algorithm. Sleep spindles were detected with high levels of sensitivity (∼83%) and precision (∼78%) and an F1-score of ∼0.81 in reference to state-of-the-art offline algorithms (which reached similar levels when compared to each other), for both naps and full nights, and largely independent of sleep scoring information. Detected spindles were comparable in frequency, duration, amplitude, and symmetry, and showed the typical time-frequency characteristics as well as a centroparietal topography. Spindles were detected close to their center and reliably at the predefined target phase. The RTSD algorithm therefore empowers researchers to target spindles during human sleep and apply the stimulation method and experimental paradigm of their choice.
Discovery of Chlorofluoroacetamide-Based Covalent Inhibitors for SARS-CoV-2 3CL Protease
Authors: Hirose Yuya , Shindo Naoya , Mori Makiko , Onitsuka Satsuki , Isogai Hikaru , Hamada Rui , Hiramoto Tadanari , Ochi Jinta , Takahashi Daisuke , Ueda Tadashi , Caaveiro Jose M.M. , Yoshida Yuya , Ohdo Shigehiro , Matsunaga Naoya , Toba Shinsuke , Sasaki Michihito , Orba Yasuko , Sawa Hirofumi , Sato Akihiko , Kawanishi Eiji , Ojida Akio
Published: June 2022

The pandemic of coronavirus disease 2019 (COVID-19) has urgently necessitated the development of antiviral agents against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The 3C-like protease (3CLpro) is a promising target for COVID-19 treatment. Here, we report the new class of covalent inhibitors for 3CLpro possessing chlorofluoroacetamide (CFA) as a cysteine reactive warhead. Based on the aza-peptide scaffold, we synthesized the series of CFA derivatives in enantiopure form and evaluated their biochemical efficiencies. The data revealed that 8a (YH-6) with R configuration at the CFA unit strongly blocks the SARS-CoV-2 replication in the infected cells and this potency is comparable to that of nirmatrelvir. The X-ray structural analysis shows that 8a (YH-6) forms a covalent bond with Cys145 at the catalytic center of 3CLpro. The strong antiviral activity and sufficient pharmacokinetics property of 8a (YH-6) suggest its potential as a lead compound for treatment of COVID-19.
Global emergence of resistance to fluconazole and voriconazole in Candida parapsilosis in tertiary hospitals in Spain during the COVID-19 pandemic
Authors: Zaragoza Oscar , Alcázar-Fuoli Laura , Trevijano-Contador Nuria , Torres-Cano Alba , Carballo-González Cristina , Puig-Asensio Mireia , Martín-Gómez María Teresa , Jiménez-Martínez Emilio , Romero Daniel , Nuvials Francesc Xavier , Olmos-Arenas Roberto , Moretó-Castellsagué María Clara , Fernández-Delgado Lucía , Rodríguez-Sevilla Graciela , Aguilar-Sánchez María-Mercedes , Ayats-Ardite Josefina , Ardanuy-Tisaire Carmen , Sanchez-Romero Isabel , Muñoz-Algarra María , Merino-Amador Paloma , González-Romo Fernando , Megías-Lobón Gregoria , García-Campos Jose Angel , Ángeles Mantecón-Vallejo María , Durán-Valle Maria Teresa , Fraile-Torres Arturo Manuel , Roiz-Mesones María Pía , Lara-Plaza Isabel , de Ayala Ana Perez , Simón-Sacristán María , Collazos-Blanco Ana , Nebreda-Mayoral Teresa , March-Roselló Gabriel
Published: June 2022

Background

Candida parapsilosis is a frequent cause of candidemia worldwide. Its incidence is associated with the use of medical implants, such as central venous catheters or parenteral nutrition. This species has reduced susceptibility to echinocandins and is susceptible to polyenes and azoles. Multiple outbreaks caused by fluconazole non-susceptible strains have been reported recently. A similar trend has been observed among the C. parapsilosis isolates received in the last two years at the Spanish Mycology Reference Laboratory.

Methods

Yeast were identified by molecular biology and antifungal susceptibility testing was performed using EUCAST protocol. ERG11 gene was sequenced to identify resistance mechanisms, and typification was carried out by microsatellite analysis.

Results

We examined the susceptibility profile of the C. parapsilosis isolates available at our Reference Laboratory since 2000 (around 1,300 strains). During the last two years, the number of isolates with acquired resistance to fluconazole and voriconazole has increased in at least eight different Spanish hospitals. Typification of the isolates revealed that some prevalent clones had spread through several hospitals of the same geographical region. One of these clones was found in hospitals from the region of Catalonia, another in hospitals from Madrid and Burgos, and two other different genotypes from Santander.

Conclusions

Our data suggests that the epidemiological situation caused by the COVID-19 pandemic might have induced a selection of fluconazole-resistant C. parapsilosis isolates that were already present at the hospitals. Further measures must be taken to avoid the establishment of clinical outbreaks that could threaten the life of infected patients.
Does place connectivity moderate the association between concentrated disadvantage and COVID-19 fatality in the United States?
Authors: Jing Fengrui , Li Zhenlong , Qiao Shan , Zhang Jiajia , Olatosi Bankole , Li Xiaoming
Published: June 2022

Concentrated disadvantaged areas have been disproportionately affected by COVID-19 outbreak in the United States (US). Meanwhile, highly connected areas may contribute to higher human movement, leading to higher COVID-19 cases and deaths. This study examined whether place connectivity moderated the association between concentrated disadvantage and COVID-19 fatality. Using COVID-19 fatality over four time periods, we performed mixed-effect negative binomial regressions to examine the association between concentrated disadvantage, Twitter-based place connectivity, and county-level COVID-19 fatality, considering potential state-level variations. Results revealed that concentrated disadvantage was significantly associated with an increased COVID-19 fatality. More importantly, moderation analysis suggested that place connectivity significantly exacerbated the harmful effect of concentrated disadvantage on COVID-19 fatality, and this significant moderation effect increased over time. In response to COVID-19 and other future infectious disease outbreaks, policymakers are encouraged to focus on the disadvantaged areas that are highly connected to provide additional pharmacological and non-pharmacological intervention policies.