BACKGROUND: Mandibular second premolar agenesis is a common problem in orthodontics and is often treated in conjunction with maxillary counterbalancing extractions. However, in cases without maxillary crowding or dental protrusion, space closure may pose challenges leading to compromised occlusal results or patient profile. Multiple techniques have been described to treat these patients; nevertheless, there is a paucity of data comparing effectiveness of space closure utilizing various anchorage techniques. The goal of this study is to assess the effectiveness of the Herbst device during mandibular molar protraction and compare it to the use of temporary anchorage device (TADs) in patients with mandibular second premolar agenesis.
METHODS: This retrospective study included 33 patients with mandibular premolar agenesis treated without maxillary extractions. Of these patients, 21 were treated with protraction Herbst devices and 12 with TADs. Changes in molar and incisor positions, skeletal base positions and occlusal plane angulations were assessed on pretreatment (T0) and post-treatment (T1) lateral cephalograms. Scans/photographs at T0 and T1 were used to evaluate canine relationship changes representing anchorage control. Space closure and breakage/failure rates were also compared. Data was analyzed with paired and unpaired t-tests at the significance level of 0.05.
RESULTS: Within the Herbst group, changes in mandibular central incisor uprighting and mandibular molar crown angulations were statistically significant. However, no significant differences were noted between the Herbst and TAD groups. Protraction rates as well as overall treatment times were comparable (0.77 mm/month vs. 0.55 mm/month and 3.02 years vs. 2.67 years, respectively). Canine relationships were maintained or improved toward a class I in 82.85% of the Herbst sample, compared to in 66.7% of the TAD sample. Emergency visits occurred in 80.1% of the Herbst group, with cementation failures or appliance breakages as the most common reasons.
CONCLUSIONS: The Herbst device could be a viable modality in cases with missing mandibular premolars where maximum anterior anchorage is desired, or if patients/parents are resistant to TADs. Furthermore, they could be beneficial in skeletal class II patients with mandibular deficiency who also need molar protraction. However, the increased incidence of emergency visits must be considered when treatment is planned.

Temporary Anchorage Devices have revolutionized our approach to anchorage management. However, their placement may carry risks, such as root perforation, damage to the periodontal ligament, buccal-nasal communication, etc. The aim of this article is to describe an original protocol in two times for the placement of a palatal mini-screw through guided surgery using a guide created by Computer-Aided Design and Manufacturing (CAD/CAM) followed by the transfer of placement information to the laboratory for the fabrication of a Custom Medical Device (CMD) for distalization.
A two-stage protocol is described and illustrated step by step. Phase 1 comprises 7 steps (including superimposition of maxillary cast and profile teleradiography, surgical tray design), followed by phase 2, which involves 3 final steps (including production of impression for laboratory, production of laboratory model with transfer of mini-screw position).
Although the position of the mini screws remains precise, a discrepancy between the planning and the intraoral situation exists. The addition of a second step therefore enables the distalization appliance to be fitted precisely and without pitfalls. Finally, this protocol ensures safe placement, making work easier for the practitioner and, ultimately, for the patient.
In a two-stage process, the placement of palatal mini screws through guided surgery using a guide created by CAD/CAM followed by the transfer of this information to the laboratory for the fabrication of a CMD for distalization proves to be a relevant approach.
Les dispositifs d’ancrage temporaires ont révolutionné notre vision de la gestion de l’ancrage. En revanche, leur mise en place peut comporter certains risques (perforation radiculaire, communication bucco-nasale, lésions vasculaires…). Cet article vise à décrire un protocole original, en deux temps, de pose de mini-vis palatine par chirurgie guidée à l’aide d’un guide réalisé par conception et fabrication assistée par ordinateur (CFAO) in-office suivie du transfert des informations de pose au laboratoire pour la confection d’un appareil de distalisation.
Un protocole en deux temps est décrit pas à pas. Le temps 1 comprend sept étapes (dont le placement virtuel des mini-vis et la création de la gouttière chirurgicale), suivi du temps 2 qui implique trois étapes (dont la réalisation de l’empreinte pour le laboratoire et l’élaboration du modèle de laboratoire avec transfert de la position des mini-vis).
Bien que la pose puisse être considérée comme précise, une différence existe entre la planification et la situation clinique. L’apport d’un second temps améliore l’adaptation de l’appareil de distalisation. Enfin, ce protocole offre une pose sécurisée et apporte ainsi un confort de travail pour le praticien et, in fine, pour le patient.
Réalisée en deux temps, la pose de mini-vis palatine par chirurgie guidée à l’aide d’un guide réalisé par CFAO in-office suivie du transfert de cette information au laboratoire pour la confection d’un appareil de distalisation s’avère être une approche pertinente.

BACKGROUND: The intertrochanteric fracture is a frequently occurring fracture, often attributed to osteoporosis in older populations. Recently, there has been a proposal to perform early surgical fixation on elderly patients to facilitate early rehabilitation. This approach has been shown to have a beneficial effect in lowering comorbidities. The study aims to compare the efficacy of the twin screw derotation type cephalomedullary nail with that of the single helical blade type cephalomedullary nail in the management of unstable intertrochanteric fractures.
METHODS:  The research sample included patients from the orthopedic outpatient and emergency departments of Adesh Medical College and Hospital, Ambala Cantt, India, who were scheduled for surgery for unstable intertrochanteric femur fractures. The patients were categorized into two groups according to the kind of implant they were given: either a twin screw derotation cephalomedullary nail or a single helical blade cephalomedullary nail. The functional result was evaluated by comparing the modified Harris hip score (HHS). Patients with unstable intertrochanteric fractures, including reverse oblique fractures and fractures with posteromedial comminution, as well as patients who provided consent, were included in this study.
RESULTS:  Thirteen individuals received treatment with proximal femoral nail antirotation (PFNA2), whereas 19 individuals received treatment with proximal femoral nail (PFN). The mean age in the PFNA2 group was 69.51, whereas the mean age in the PFN group was 70.804. There were three patients in the PFNA2 group and five patients in the PFN group who had a tip apex distance of more than 25 mm. According to the Cleveland index, nine patients in the PFNA2 group and eight patients in the PFN group had an implant location that was not optimum. Four patients in the PFNA2 group and seven patients in the PFN group had a neck shaft angle difference of more than 10° between their undamaged and operated sides. The mean HHS was 74.55 for the PFNA2 group and 69.88 for the PFN group. The PFNA2 group exhibited four problems, whereas the PFN group had five issues.
CONCLUSIONS:  The study found that both implants offer similar functional outcomes, with adherence to specific radiological parameters optimizing results. While both face similar challenges with osteoporosis, there was no notable distinction between them. Notably, the PFNA2 group showed superior outcomes in perioperative morbidity.

Within the three-dimensional (3D) nuclear space, the genome organizes into a series of orderly structures that impose important influences on gene regulation. T lymphocytes, crucial players in adaptive immune responses, undergo intricate transcriptional remodeling upon activation, leading to differentiation into specific effector and memory T cell subsets. Recent evidence suggests that T cell activation is accompanied by dynamic changes in genome architecture at multiple levels, providing a unique biological context to explore the functional relevance and molecular mechanisms of 3D genome organization. Here, we summarize recent advances that link the reorganization of genome architecture to the remodeling of transcriptional programs and conversion of cell fates during T cell activation and differentiation. We further discuss how various chromatin architecture regulators, including CCCTC-binding factor and several transcription factors, collectively modulate the genome architecture during this process.

Genome organization can regulate gene expression and promote cell fate transitions. The differentiation of germline stem cells (GSCs) to oocytes in Drosophila involves changes in genome organization mediated by heterochromatin and the nuclear pore complex (NPC). Heterochromatin represses germ cell genes during differentiation, and NPCs anchor these silenced genes to the nuclear periphery, maintaining silencing to allow for oocyte development. Surprisingly, we found that genome organization also contributes to NPC formation, mediated by the transcription factor Stonewall (Stwl). As GSCs differentiate, Stwl accumulates at boundaries between silenced and active gene compartments. Stwl at these boundaries plays a pivotal role in transitioning germ cell genes into a silenced state and activating a group of oocyte genes and nucleoporins (Nups). The upregulation of these Nups during differentiation is crucial for NPC formation and further genome organization. Thus, cross-talk between genome architecture and NPCs is essential for successful cell fate transitions.

Mechanisms of X chromosome dosage compensation have been studied extensively in a few model species representing clades of shared sex chromosome ancestry. However, the diversity within each clade as a function of sex chromosome evolution is largely unknown. Here, we anchor ourselves to the nematode Caenorhabditis elegans, for which a well-studied mechanism of dosage compensation occurs through a specialized structural maintenance of chromosomes (SMC) complex, and explore the diversity of dosage compensation in the surrounding phylogeny of nematodes. Through phylogenetic analysis of the C. elegans dosage compensation complex and a survey of its epigenetic signatures, including X-specific topologically associating domains (TADs) and X-enrichment of H4K20me1, we found that the condensin-mediated mechanism evolved recently in the lineage leading to Caenorhabditis through an SMC-4 duplication. Intriguingly, an independent duplication of SMC-4 and the presence of X-specific TADs in Pristionchus pacificus suggest that condensin-mediated dosage compensation arose more than once. mRNA-seq analyses of gene expression in several nematode species indicate that dosage compensation itself is ancestral, as expected from the ancient XO sex determination system. Indicative of the ancestral mechanism, H4K20me1 is enriched on the X chromosomes in Oscheius tipulae, which does not contain X-specific TADs or SMC-4 paralogs. Together, our results indicate that the dosage compensation system in C. elegans is surprisingly new, and condensin may have been co-opted repeatedly in nematodes, suggesting that the process of evolving a chromosome-wide gene regulatory mechanism for dosage compensation is constrained.
UNASSIGNED: X chromosome dosage compensation mechanisms evolved in response to Y chromosome degeneration during sex chromosome evolution. However, establishment of dosage compensation is not an endpoint. As sex chromosomes change, dosage compensation strategies may have also changed. In this study, we performed phylogenetic and epigenomic analyses surrounding Caenorhabditis elegans and found that the condensin-mediated dosage compensation mechanism in C. elegans is surprisingly new, and has evolved in the presence of an ancestral mechanism. Intriguingly, condensin-based dosage compensation may have evolved more than once in the nematode lineage, the other time in Pristionchus. Together, our work highlights a previously unappreciated diversity of dosage compensation mechanisms within a clade, and suggests constraints in evolving new mechanisms in the presence of an existing one.

BACKGROUND: Cotton is a major world cash crop and an important source of natural fiber, oil, and protein. Drought stress is becoming a restrictive factor affecting cotton production. To facilitate the development of drought-tolerant cotton varieties, it is necessary to study the molecular mechanism of drought stress response by exploring key drought-resistant genes and related regulatory factors.
RESULTS: In this study, two cotton varieties, ZY007 (drought-sensitive) and ZY168 (drought-tolerant), showing obvious phenotypic differences under drought stress, were selected. A total of 25,898 drought-induced genes were identified, exhibiting significant enrichment in pathways related to plant stress responses. Under drought induction, At subgenome expression bias was observed at the whole-genome level, which may be due to stronger inhibition of Dt subgenome expression. A gene co-expression module that was significantly associated with drought resistance was identified. About 90% of topologically associating domain (TAD) boundaries were stable, and 6613 TAD variation events were identified between the two varieties under drought. We identified 92 genes in ZY007 and 98 in ZY168 related to chromatin 3D structural variation and induced by drought stress. These genes are closely linked to the cotton response to drought stress through canonical hormone-responsive pathways, modulation of kinase and phosphatase activities, facilitation of calcium ion transport, and other related molecular mechanisms.
CONCLUSIONS: These results lay a foundation for elucidating the molecular mechanism of the cotton drought response and provide important regulatory locus and gene resources for the future molecular breeding of drought-resistant cotton varieties.

BACKGROUND: Multiple studies have demonstrated a negative correlation between gene expression and positioning of genes at the nuclear envelope (NE) lined by nuclear lamina, but the exact relationship remains unclear, especially in light of the highly stochastic, transient nature of the gene association with the NE.
RESULTS: In this paper, we ask whether there is a causal, systematic, genome-wide relationship between the expression levels of the groups of genes in topologically associating domains (TADs) of Drosophila nuclei and the probabilities of TADs to be found at the NE. To investigate the nature of this possible relationship, we combine a coarse-grained dynamic model of the entire Drosophila nucleus with genome-wide gene expression data; we analyze the TAD averaged transcription levels of genes against the probabilities of individual TADs to be in contact with the NE in the control and lamins-depleted nuclei. Our findings demonstrate that, within the statistical error margin, the stochastic positioning of Drosophila melanogaster TADs at the NE does not, by itself, systematically affect the mean level of gene expression in these TADs, while the expected negative correlation is confirmed. The correlation is weak and disappears completely for TADs not containing lamina-associated domains (LADs) or TADs containing LADs, considered separately. Verifiable hypotheses regarding the underlying mechanism for the presence of the correlation without causality are discussed. These include the possibility that the epigenetic marks and affinity to the NE of a TAD are determined by various non-mutually exclusive mechanisms and remain relatively stable during interphase.
CONCLUSIONS: At the level of TADs, the probability of chromatin being in contact with the nuclear envelope has no systematic, causal effect on the transcription level in Drosophila. The conclusion is reached by combining model-derived time-evolution of TAD locations within the nucleus with their experimental gene expression levels.

BACKGROUND: The targeted axillary dissection (TAD) procedure is used in clinically positive lymph node (cN+) breast cancer to assess whether pathological complete response (pCR) is achieved after neoadjuvant systemic therapy (NST) to decide on de-escalation of axillary lymph node dissection (ALND). In this study, we review the implementation of the TAD procedure in a large regional breast cancer center.
METHODS: All TAD procedures between 2016 and 2022 were reviewed. The TAD procedure consists of marking pre-NST the largest suspected metastatic lymph node(s) using a radioactive I-125 seed. During surgery, the marked node was excised together with a sentinel node procedure. Axillary therapy (ALND, axillary radiotherapy, or nothing) recommendations were based on the amount of suspected positive axillary lymph nodes (ALNs < 4 or ≥ 4) pre-NST and if pCR was achieved after NST.
RESULTS: A total of 312 TAD procedures were successfully performed in 309 patients. In 134 (43%) cases, pCR of the TAD lymph nodes were achieved. Per treatment protocol, 43 cases (14%) did not receive any axillary treatment, 218 cases (70%) received adjuvant axillary radiotherapy, and 51 cases (16%) underwent an ALND. During a median follow-up of 2.8 years, 46 patients (14%) developed recurrence, of which 11 patients (3.5%) had axillary recurrence.
CONCLUSIONS: Introduction of the TAD procedure has resulted in a reduction of 84% of previously indicated ALNDs. Moreover, 18% of cases did not receive adjuvant axillary radiotherapy. These data show that implementation of de-escalation axillary treatment with the TAD procedure appeared to be successful.

BACKGROUND: Lateral fractures of proximal femur are the most frequent fractures in elderly people. Internal fixation using medullary nails is the gold standard of treatment (Gamma 3 nail is the most implanted device) due to reduced incidence of complications than other devices. We report our experience in treating this kind of fractures with Gamma 3 nail, between January 2015 and December 2021.
METHODS: We performed a retrospective cohort study of patients treated in our orthopaedic department; level of clinical care is III: 559 patients (431 females and 128 males, with an average age of 85.3 years) with lateral femoral neck fracture. All patients were surgically treated with Gamma 3 standard nail (SGN). We evaluated preliminary X-rays to classify fractures, according to AO-OTA classification and post-operative X-ray to verify cephalic screw position site, according to areas described by Cleveland in 1959: we measured tip-to-apex distance (TAD) and tip-to-apex calcar referred distance (CalTAD). Finally Chang reduction quality criteria (CRQC) for fracture reduction of trochanteric fractures were determined using preoperative or postoperative Antero-Posterior (AP) and lateral radiographs in a Picture Archiving and Communication System (PACS). Incidence of cut-out was evaluated in relation with these parameters. Patients were divided into 2 groups: first group had cephalic screw in optimal positions (5-8-9), the other group had cephalic screw in other positions.
RESULTS: In 328 patients (58.7%) screw was in positions 5-8-9, in 231 patients (41.2%) screw was in not-optimal position. Median TAD was 19.1 ± 7.0 mm (range = 0.0-50.5); in 463 patients (82.8%) TAD was ≤ 25 mm. Median CalTAD was 21.4 ± 4.7 mm (range = 5.7-39.2); in 105 patients (79.4%) CalTAD was ≤ 25 mm. Cut-out was observed in 8 cases (1.43%). Multivariate analysis showed a significant correlation (p < 0,05) between incidence of cut-out and fracture type 31A2 and with TAD values >25 mm. Cephalic screw position did not influence incidence of cut-out.
CONCLUSIONS: In order to obtain fracture healing with a low risk of failure, in particular cut-out, it is necessary to obtain good reduction of fracture and optimal lag screw position in order to achieve a TAD inferior to 25 mm.