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Hematopoietic stem cell (HSC) regeneration is the remarkable process by which extremely rare, normally inactive cells of the bone marrow can replace an entire organ if called to do so by injury or harnessed by transplantation. HSC research is arguably the first quantitative single-cell science and the foundation of adult stem cell biology. Bone marrow transplant is the oldest and most refined technique of regenerative medicine. Here we review the intertwined history of the discovery of HSCs and bone marrow transplant, the molecular and cellular mechanisms of HSC self-renewal, and the use of HSCs and their derivatives for cell therapy.

Microscopy and genomic approaches provide detailed descriptions of the three-dimensional folding of chromosomes and nuclear organization. The fundamental question is how activity of molecules at the nanometer scale can lead to complex and orchestrated spatial organization at the scale of chromosomes and the whole nucleus. At least three key mechanisms can bridge across scales: (1) tethering of specific loci to nuclear landmarks leads to massive reorganization of the nucleus; (2) spatial compartmentalization of chromatin, which is driven by molecular affinities, results in spatial isolation of active and inactive chromatin; and (3) loop extrusion activity of SMC (structural maintenance of chromosome) complexes can explain many features of interphase chromatin folding and underlies key phenomena during mitosis. Interestingly, many features of chromosome organization ultimately result from collective action and the interplay between these mechanisms, and are further modulated by transcription and topological constraints. Finally, we highlight some outstanding questions that are critical for our understanding of nuclear organization and function. We believe many of these questions can be answered in the coming years.

The regenerative capacity of the vertebrate retina varies substantially across species. Whereas fish and amphibians can regenerate functional retina, mammals do not. In this perspective piece, we outline the various strategies nonmammalian vertebrates use to achieve functional regeneration of vision. We review key differences underlying the regenerative potential across species including the cellular source of postnatal progenitors, the diversity of cell fates regenerated, and the level of functional vision that can be achieved. Finally, we provide an outlook on the field of engineering the mammalian retina to replace neurons lost to injury or disease.

Dramatic nuclear reorganization occurs during early development to convert terminally differentiated gametes to a totipotent zygote, which then gives rise to an embryo. Aberrant epigenome resetting severely impairs embryo development and even leads to lethality. How the epigenomes are inherited, reprogrammed, and reestablished in this critical developmental period has gradually been unveiled through the rapid development of technologies including ultrasensitive chromatin analysis methods. In this review, we summarize the latest findings on epigenetic reprogramming in gametogenesis and embryogenesis, and how it contributes to gamete maturation and parental-to-zygotic transition. Finally, we highlight the key questions that remain to be answered to fully understand chromatin regulation and nuclear reprogramming in early development.

The article deals with such an interesting and rather complex, multidimensional phenomenon as lacuna on the material of three unrelated languages-Russian, Azerbaijani and English. The lexical lacunae are systematized and analyzed on the following groups: motivated and non-motivated lacunae. Motivated lacuna is connected with the following fact: the native speakers of the other languages do not have this reality idea. Such lacuna can be revealed in the field of the unequal lexeme. However, non-motivated lacuna is not explained by the absence of the idea. The idea exists, but the native speakers of the other languages did not call it owing to the certain cultural, mental, geographical, social, psychological or other reasons. Perhaps, they did not attach importance to them. So, non-motivated lacunae are considered on the concrete lexical-semantic groups in the article :1. Family relationship terms which are divided into two groups: a) blood relations; b) marital relationship. It should be noted that there are no special terms of marital relationship in English unlike Russian and Azerbaijani. The terms of blood relations are used together with the word “law” in postposition in order to denote the necessary marital relationship in English. 2. Nature: natural phenomena, flora and fauna. This group includes a lot of various lacunae connected with nature, natural phenomena. Such lacunae are caused by such objective factors as features of landscape, climatic conditions, relief, predominance of concrete animal, bird, insect, fish species etc. Certainly, the main factor is concrete people’s perception of nature, natural phenomena. Perception of the world influences nomination, highlighting specific natural objects taking into account the degree of their importance. When studying lacunae it is important to take into consideration both extra- and intralinguistic factors.

Lamins interact with a host of nuclear membrane proteins, transcription factors, chromatin regulators, signaling molecules, splicing factors, and even chromatin itself to form a nuclear subcompartment, the nuclear lamina, that is involved in a variety of cellular processes such as the governance of nuclear integrity, nuclear positioning, mitosis, DNA repair, DNA replication, splicing, signaling, mechanotransduction and -sensation, transcriptional regulation, and genome organization. Lamins are the primary scaffold for this nuclear subcompartment, but interactions with lamin-associated peptides in the inner nuclear membrane are self-reinforcing and mutually required. Lamins also interact, directly and indirectly, with peripheral heterochromatin domains called lamina-associated domains (LADs) and help to regulate dynamic 3D genome organization and expression of developmentally regulated genes.

The airways are frequently involved in nonneoplastic lung diseases, and sometimes their involvement dominates the clinical picture. In these situations, the combination of clinical and radiologic findings is sometimes sufficient to reach a firm diagnosis; however, in a significant proportion of cases a biopsy is obtained, frequently representing a challenge for the practicing pathologists. In the present chapter, beside the description of some well defined entities, we present the most relevant morphologic features that can be encountered on small endoscopic biopsies and on surgical samples, trying to identify the elementary lesions and to correlate them with the complexity of the different clinical settings where they can be found. It is a rare case in which the morphological features are diagnostic per se of a specific disease. Conversely, the identification of a few key elementary lesions can be of help to narrow the differential diagnoses that can be offered to clinicians to complete the difficult puzzle of interstitial lung diseases.

• An understanding of thyroid embryogenesis and the physiology of the thyroid gland in the perinatal period is important for proper interpretation of abnormal laboratory results and initiation of appropriate treatment. • Appropriate thyroid hormone function is essential for normal neurodevelopment in infancy and childhood. Hypothyroidism in the first year of life can result in significant deleterious effects on growth and neurologic injury. • Delay in treatment of congenital hypothyroidism (CH) is the most common preventable cause of mental retardation. • Neonatal screening can provide early diagnosis and can prevent delays in treatment. Newborn screening methods differ and may possibly miss rare forms of congenital hypothyroidism. • Eighty-five percent of cases of permanent CH are associated with abnormal development of the thyroid gland. • In preterm newborns, thyroid hormone levels may fall because of immaturity of the thyroid gland, but these changes may be exacerbated by complications of prematurity. • Thyroid metabolism can be affected by exogenous sources of iodine, dopamine infusions, blood transfusion, and glucocorticoid treatment. • The clinical manifestations of Graves disease in the newborn include irritability, flushing, diarrhea, vomiting, tachycardia, hypertension, poor weight gain, thyroid enlargement, and exophthalmos. • There is concern for neurologic damage in infants with hemangiomas when hypothyroidism is occult and untreated.

• The placenta is the first organ to form in mammals and is required for establishment of a maternal–fetal vascular interface capable of supplying the bioenergetic needs of the developing conceptus. • Multiple placental cell types engage in highly varied functions, from attachment, invasion, and vascular remodeling to cell fusion, hormone production, and nutrient transport. • Multiple mechanisms allow transport of waste and nutrients across the placenta, including diffusion, transporter protein-mediated (facilitated diffusion and active transporters), and receptor-mediated mechanisms. • The placenta is not an inert transport interface. It consumes 40%–60% of the oxygen and glucose delivered to the uterus at term. Thus conditions that alter placental metabolism can indirectly affect nutrient transport to the fetus. • Maternal and fetal health alter placental function, which in turn influences fetal adaptations and contributes to in utero fetal programming. • Abnormal placentation and placental infections can lead to preeclampsia (PE), fetal growth retardation, or preterm birth, which can have lifelong bearing on health. • In the United States, iatrogenic delivery is responsible for almost half the births that occur between 28 and 37 weeks of gestation, primarily caused by placental pathologies such as PE or intrauterine growth restriction. • Efforts to standardize placental examination after delivery are in progress so that connections between specific placental problems and poor outcomes can be better defined. In parallel, new advanced imaging techniques and biomarkers for placental function are being developed.

Chronic diffuse lung diseases involve a spectrum of nonneoplastic inflammatory conditions that affect the lung parenchyma. This chapter reviews the spectrum of disease including idiopathic interstitial pneumonias, pulmonary manifestations of systemic collagen vascular disease, diffuse eosinophilc lung disease, drug-associated lung disease, diffuse granulomatous lung disease, and a variety of miscellaneous diseases that defy classification. Individual entities are reviewed, followed by a section highlighting a practical approach to the four most common patterns of injury encountered in practice.

This review identifies the three-dimensional knee loads that have the highest risk of injuring the anterior cruciate ligament (ACL) in the athlete. It is the combination of the muscular resistance to a large knee flexion moment, an external reaction force generating knee compression, an internal tibial torque, and a knee abduction moment during a single-leg athletic manoeuvre such as landing from a jump, abruptly changing direction, or rapidly decelerating that results in the greatest ACL loads. While there is consensus that an anterior tibial shear force is the primary ACL loading mechanism, controversy exists regarding the secondary order of importance of transverse-plane and frontal-plane loading in ACL injury scenarios. Large knee compression forces combined with a posteriorly and inferiorly sloped tibial plateau, especially the lateral plateau-an important ACL injury risk factor-causes anterior tibial translation and internal tibial rotation, which increases ACL loading. Furthermore, while the ACL can fail under a single supramaximal loading cycle, recent evidence shows that it can also fail following repeated submaximal loading cycles due to microdamage accumulating in the ligament with each cycle. This challenges the existing dogma that non-contact ACL injuries are predominantly due to a single manoeuvre that catastrophically overloads the ACL.

Background Thumb carpometacarpal (CMC) joint arthroplasty is a common procedure in the surgical management of symptomatic thumb basal joint arthritis. Following trapeziectomy, a number of suspensionplasty techniques are often used, but limited comparative evidence exists between these techniques. The central aim of this study was to prospectively compare the outcomes of 2 suspensionplasty techniques following trapeziectomy: suture button (TightRope) versus ligament reconstruction and tendon interposition (LRTI). Methods Prospective data were collected on 112 consecutive patients with Eaton stage III-IV thumb CMC arthritis who underwent open trapeziectomy and suspensionplasty. There were 53 LRTI and 59 TightRope suspensionplasty procedures. Outcomes were measured using the Quick Disabilities of the Arm, Shoulder, and Hand ( QuickDASH) questionnaire, Visual Analogue Scale (VAS) for pain, radiographic analysis, and lateral pinch strength. Patient demographic data and complications were also recorded. Results Patients undergoing TightRope suspensionplasty had significantly higher trapeziometacarpal index and thus less subsidence than the LRTI group at 2 weeks (0.22 vs 0.17 [ P < .0001]) and 3 months (0.17 vs 0.15 [ P < .05]) postoperatively. TightRope suspensionplasty also had a significantly lower QuickDASH score at 2 weeks (64.7 vs 74.6 [ P < .05]), 3 months (20.7 vs 32.5 [ P < .05]), and 1 year postoperatively (7.57 vs 21.5 [ P < .05]) compared with the LRTI group. However, there was no difference in VAS pain, lateral pinch strength, reoperation, or complications at any time point between groups. Conclusions Thumb CMC joint arthroplasty performed with a TightRope suspensionplasty versus LRTI yielded short-term improved resistance to subsidence, long-term greater improvement in clinical outcome by QuickDASH, and no difference in pain or complication rates.

Optimal specimen handling is essential for the accurate interpretation of biopsies and cytologic preparations obtained in the course of evaluating the patient with lung disease. Sampling techniques available include bronchoscopy, transthoracic needle core biopsy or aspiration, and surgical wedge biopsy of peripheral lung through a transthoracic approach. In this chapter specimen characteristics and processing steps are presented for each of the common lung samples taken in the course of clinical evaluation for pulmonary disease. Also, for each type of sample the benefits and limitations are reviewed. Such a working knowledge of specimen handling for each procedure ensures the greatest likelihood of success in establishing a specific diagnosis and, in the end, a rational treatment plan. The addition of clinical information dramatically increases the likelihood of a meaningful and accurate pathologic diagnosis, especially in the setting of biopsies for diffuse lung disease (interstitial lung disease).

• Infants born with ambiguous genitalia or nonpalpable testes need to be evaluated for congenital adrenal hyperplasia as it can be life threatening. • Adrenal steroid levels vary with gestational age. • Adrenal insufficiency should be treated with hydrocortisone to avoid adrenal crisis. High doses of hydrocortisone contain mineralocorticoid activity.

Cystic hydatid disease or cystic echinococcosis (CE) is a globally endemic zoonosis caused by the larval cyst stage of the tapeworm Echinococcus granulosus. Concomitant presence of CE and hepatocellular carcinoma (HCC) is a rare clinical scenario. A 70-year-old male patient presented with acute abdominal pain to the surgical outpatient department. On evaluation, a cystic lesion with solid components and free fluid in the abdomen was observed, which led to multiple differentials in the working diagnosis. A CT showed the mass to have a delayed enhancement. Surgical exploration revealed a partially ruptured hydatid cyst with daughter cysts in the abdominal cavity and a solid-component mass lesion. We proceeded with a right partial hepatectomy. Pathological evaluation revealed a pale mass lesion with a large collapsed cyst. HCC with unusual dense fibrillar fibrosis and cystic interface with normal parenchyma was observed. This case connects the multimodal assessment of radiology, surgery and pathology.

The formation of an intraperitoneal pseudocyst as a complication of ventriculoperitoneal shunts is well known. However, the formation of a pseudocyst at the subcutaneous extraperitoneal abdominal space is unusual and likely secondary to the migration of the peritoneal catheter. We present a 53-year-old male who had placement of a ventriculoperitoneal shunt for hydrocephalus secondary to a vestibular schwannoma. Five months later, he presented with an enormously distended abdomen. Investigations showed the peritoneal catheter in the extraperitoneal space within a large right lower quadrant abdominal wall pseudocyst. The patient was taken to the operating theatre, and the shunt was externalised at the original abdominal incision. Approximately 3 L of cerebrospinal fluid were aspirated from the distal peritoneal catheter. After negative cultures, a new peritoneal catheter was placed intraperitoneally at the contralateral lower abdominal quadrant. The contralateral quadrant was utilised to prevent fluid accumulation into the old extraperitoneal cavity.

Uterine rupture can be associated with severe maternal and neonatal morbidity and mortality. It should be considered as a differential diagnosis in all pregnant women who present with acute abdomen, haemoperitoneum and have specific risk factors, even during the first trimester. This is a case report of a 25-year-old woman who presented to emergency department with abdominal pain and vaginal bleeding at approximately 6–8 weeks gestation. She developed an acute surgical abdomen and required urgent surgical management. Despite intervention, she had massive haemorrhage, disseminate intravascular coagulation, admission to intensive care unit and prolonged hospital stay as complications. Posterior uterine wall rupture while rare, must be considered as a differential diagnosis as early intervention is crucial to prevent bad outcomes.

Background Distal-ulna stump (DUS) instability often occurs when performing a distal radioulnar joint (DRUJ) arthroplasty. Recent studies suggest that the distal interosseous membrane (DIOM) reinforces the triangular fibrocartilage complex, providing additional stability to the DRUJ. The aim of this study was to determine whether the DIOM stabilizes the ulnar stump. Methods Twenty fresh-frozen random forearms were dissected. The presence of a distal oblique bundle (DOB) was recorded and measured. The radius was fixed to a vise and the ulna kept free. The DRUJ was fixed with a lag screw. A bone slice was removed by transverse ulna osteotomies 10 and 15 mm proximal to the DRUJ. A 10-N force was applied to the ulna in dorsal and volar directions. Displacements were measured. The DIOM was then transected, and maneuvers and measurements were repeated and compared. Results A distinct distal membrane was present in 70% and a cord-like DOB in 30%. The mean length was 29 mm. Its origin was proximal to the sigmoid notch; its insertion was on the distal third of the ulna, at its lateral border. This attachment is comprised between 39 and 48 mm proximal to the ulnocarpal joint. Initial displacements averaged 22 mm dorsally and 13 mm volarly. After DIOM transection, ulnar translocation increased to 31 mm dorsally and 19 mm volarly. Conclusion In DRUJ arthroplasties, the DIOM does not appear to be a stabilizer of the DUS beneath a useful threshold. Its retaining effect occurs only after an initial 22-mm dorsal displacement, which we consider not clinically admissible. Therefore, in DRUJ arthroplasties, some augmentation might be advisable.

Studying the placenta can provide information about the mechanistic pathways of pregnancy disease. However, analyzing placental tissues and manipulating placental function in real-time during pregnancy is not feasible. The ex vivo placental perfusion model allows observing important aspects of the physiology and pathology of the placenta, while maintaining its viability and functional integrity, and without causing harm to mother or fetus. In this review, we describe and compare setups for this technically complex model and summarize outcomes from various published studies. We hope that our review will encourage wider use of ex vivo placental perfusion, which in turn would generate more knowledge to improve pregnancy outcomes.

Mandibular fractures are rare in infants, and diagnosis can be easily missed due to the difficulty in obtaining an adequate history and the subtle signs. A high index of suspicion and detailed history taking from the caregiver are mandatory to pick up these cases.There are a plethora of management options that have been reported in dealing with such fractures. They range from conservative management to internal fixation by absorbable plates. While conservative management does not interfere with mandibular growth and teeth development, any surgical intervention can carry this risk. Nevertheless, a severely displaced fracture may need anatomical reduction and fixation to allow early nutrition.This study reports a 3-month-old male infant with a fracture in the mandibular symphysis who underwent reduction of the fracture and circummandibular fixation using immobilisation by an acrylic splint for 4 weeks. His long-term follow-up after 20 months showed adequate dentition with proper healing of the fracture site.

Purpose To describe the use of glycerine in improving media clarity in cases with edematous cornea. Methods Retrospective case-series including patients with posterior segment pathologies needing surgical invention and having corneal edema. Each case was studied for the role of topical application of glycerine instead of viscoelastic agents and the course of surgery. The cases were followed up for minimum 3-months duration. Results Six cases with corneal edema having posterior segment pathology underwent surgery with intraoperative topical application of glycerine. The corneal edema was seen to clear with progression of surgery and was maintained until the end of surgery. Procedures like vitreoretinal surgery, identification of break, internal limiting membrane peeling, intraocular lens explantation, scleral indentation, DSEK graft removal, and subretinal band removal could be performed in these cases. Conclusion Intraoperative glycerine use during vitreoretinal surgeries is helpful in improving the corneal clarity and maintaining it till the end of surgery.

The body responds to changing circumstances and environmental threats both consciously and subconsciously. The cognitive response to a physical threat normally involves movement mediated by skeletal muscle. There are a number of control mechanisms ‘hardwired’ into the nervous system which enable muscle systems to respond in an integrated fashion without involving a conscious decision, although the subject is usually conscious of what has happened. These include the stretch reflex, the withdrawal reflex and the crossed extensor reflexes. Muscle spindles, Golgi tendon organs and cutaneous nociceptors provide the sensory input to these reflexes, and muscle spindles also play a role in the control of voluntary movement. The autonomic nervous system controls the internal environment in response to environmental change. It consists of the parasympathetic division, which controls basal and vegetative mechanisms, and the sympathetic nervous system, which controls visceral adaptive responses to any sort of environmental change or threat.

Fibroblasts play an important role in maintaining tissue integrity by secreting components of the extracellular matrix and initiating response to injury. Although the function of fibroblasts has been extensively studied in adults, the embryonic origin and diversification of different fibroblast subtypes during development remain largely unexplored. Using zebrafish as a model, we show that the sclerotome, a sub-compartment of the somite, is the embryonic source of multiple fibroblast populations, including tenocytes (tendon fibroblasts), blood vessel associated fibroblasts, and fin mesenchymal cells. High resolution imaging shows that different fibroblast subtypes occupy unique anatomical locations with distinct morphologies. Photoconversion-based cell lineage analysis reveals that sclerotome progenitors at different dorsal-ventral and anterior-posterior positions display distinct differentiation potentials. Single cell clonal analysis suggests that sclerotome progenitors are multipotent, and the fate of their daughter cells is biased by their migration paths and relative positions. Using a small molecule inhibitor, we show that BMP signaling is required for the development of fin mesenchymal cells in the peripheral fin fold. Together, our work demonstrates that the sclerotome contains multipotent progenitors that respond to local signals to generate a diverse population of tissue-resident fibroblasts. AUTHOR SUMMARY Fibroblasts are present in most organs in our body. They not only provide structural support to corresponding tissues, but also play important roles in wound healing and tissue fibrosis. Although the function of fibroblasts has been well appreciated, how different tissue-resident fibroblasts emerge during embryonic development is still poorly understood. Using the zebrafish model, we identify the sclerotome, a sub-compartment of the embryonic somite, as the main source of multiple fibroblast populations. Different fibroblast subtypes display distinct morphologies and locate at unique positions to support different tissues, including the muscles, blood vessels and the fin fold. Using cell tracing in live animals, we find that single sclerotome progenitors are able to generate more than one type of fibroblasts. The differentiation potential of sclerotome progenitors is biased by their initial locations in the trunk as well as their migration directions and relative positions. Local BMP signaling in the fin fold is essential for the proper development of sclerotome derived fin mesenchymal cells. Together, our results show that local microenvironment contributes to the diversification of multipotent sclerotome progenitors into distinct fibroblast subtypes.

BACKGROUND: Central histamine (HA) signaling modulates diverse cortical and subcortical circuits throughout the brain, including the nucleus accumbens (NAc). The NAc, a key striatal subregion directing reward-related behavior, expresses diverse HA receptor subtypes that elicit cellular and synaptic plasticity. However, the neuromodulatory capacity of HA within interneuron microcircuits in the NAc remains unknown. METHODS: We combined electrophysiology, pharmacology, voltammetry, and optogenetics in male transgenic reporter mice to determine how HA influences microcircuit motifs controlled by parvalbumin-expressing fast-spiking interneurons (PV-INs) and tonically active cholinergic interneurons (CINs) in the NAc shell. RESULTS: HA enhanced CIN output through an H(2) receptor (H(2)R)-dependent effector pathway requiring Ca(2+)-activated small-conductance K(1) channels, with a small but discernible contribution from H(1)Rs and synaptic H(3)Rs. While PV-IN excitability was unaffected by HA, presynaptic H(3)Rs decreased feedforward drive onto PV-INs via AC-cAMP-PKA (adenylyl cyclase-cyclic adenosine monophosphate-protein kinase A) signaling. H(3)R-dependent plasticity was differentially expressed at mediodorsal thalamus and prefrontal cortex synapses onto PV-INs, with mediodorsal thalamus synapses undergoing HA-induced long-term depression. These effects triggered downstream shifts in PV-IN- and CIN-controlled microcircuits, including near-complete collapse of mediodorsal thalamus-evoked feedforward inhibition and increased mesoaccumbens dopamine release. CONCLUSIONS: HA targets H-|R, H(2)R, and H(3)Rs in the NAc shell to engage synapse- and cell type-specific mechanisms that bidirectionally regulate PV-IN and CIN microcircuit activity. These findings extend the current conceptual framework of HA signaling and offer critical insight into the modulatory potential of HA in the brain.

Purpose To highlight a case of chorioretinitis sclopetaria, with concomitant macular hole formation and orbital emphysema, caused by a commercial-grade pressure washer. Patient A 19-year-old male presented to the emergency department with a left eye injury, incurred after being sprayed with a commercial-grade pressure washer. He endorsed ipsilateral blurred vision, pain, and linear floaters. Left eye visual acuity was 20/40. Dilated fundus exam showed inferior vitreous hemorrhage, retinal whitening, and pre-, intra-, and sub-retinal hemorrhages, consistent with chorioretinitis sclopetaria. Optical coherence tomography revealed a full-thickness macular hole. Computed tomography scan of the orbits showed subcutaneous and post-septal orbital emphysema. Two months following injury, vitreous and retinal hemorrhages and macular hole resolved. Five months following injury, visual acuity improved to 20/20. Discussion Chorioretinitis sclopetaria is defined as a full-thickness chorioretinal disruption resulting from a high-velocity projectile passing adjacent to or into the orbit without penetrating the globe. Chorioretinal deformation and ocular comorbidities are influenced by the velocity of the missile and its spatial relationship to the orbit. While this pattern of injury is typically associated with indirect trauma to the globe by a BB or a bullet, this is the first report of chorioretinitis sclopetaria precipitated by a high-velocity liquid missile.

Purpose To describe with multimodal imaging including the use of ultra-widefield optical coherence tomography (OCT) imaging a distinct phenotype of autosomal recessive nanophthalmos associated with a novel mutation of the MFRP gene (membrane-type frizzled-related protein). Methods Case report and review of the relevant literature. Patients Single patient followed by the Weill Cornell Medicine Department of Ophthalmology Retina and Glaucoma Services. Results A patient with a novel homozygous mutation in the MFRP gene (c.472C>T) presented with nanophthalmos, optic disc drusen, foveal hypoplasia, and extensive peripheral retinoschisis, which was revealed to be multilevel retinoschisis on ultra-wide field OCT. Unlike other reported cases, the findings associated with this novel mutation did not include foveoschisis nor clinically obvious retinitis pigmentosa. The patient underwent prophylactic peripheral laser iridotomy in both eyes. Conclusion Here we present a patient with nanophthalmos, optic disc drusen, and foveal hypoplasia associated with extensive peripheral retinoschisis imaged by ultra-widefield OCT, but not foveal retinoschisis or prominent retinitis pigmentosa. The findings may expand the clinical spectrum of MFRP-associated nanophthalmos.

Background The aim of this study was to review, systematically, evidence concerning the link between the ACTN3 R577X polymorphism and the rates and severity of non-contact injuries and exercise-induced muscle damage in athletes and individuals enrolled in exercise training programs. Methods A computerized literature search was performed in the electronic databases PubMed, Web of Science, and SPORTDiscus, from inception until November 2020. All included studies compared the epidemiological characteristics of non-contact injury between the different genotypes of the ACTN3 R577X polymorphism. Results Our search identified 492 records. After the screening of titles, abstracts, and full texts, 13 studies examining the association between the ACTN3 genotypes and the rate and severity of non-contact injury were included in the analysis. These studies were performed in 6 different countries (Spain, Japan, Brazil, China, Republic of Korea, and Italy) and involved a total participant pool of 1093 participants. Of the studies, 2 studies involved only women, 5 studies involved only men, and 6 studies involved both men and women. All the studies included were classified as high-quality studies (≥6 points in the Physiotherapy Evidence Database (PEDro) scale score). Overall, evidence suggests there is an association between the ACTN3 R577X genotype and non-contact injury in 12 investigations. Six studies observed a significant association between ACTN3 R577X polymorphism and exercise induced muscle damage: two with non-contact ankle injury, three with non-contact muscle injury, and one with overall non-contact injury. Conclusion The present findings support the premise that possessing the ACTN3 XX genotype may predispose athletes to a higher probability of some non-contact injuries, such as muscle injury, ankle sprains, and higher levels of exercise-induced muscle damage.

Statement of problem Knowledge about the location and dimensions of the mental foramen is important for surgical planning and implant placement in the posterior mandibular region. Purpose The purpose of this clinical study was to assess the location and dimensions of the mental foramen in individuals of different facial type, skeletal class, and sex by means of cone beam computed tomography (CBCT) images. Material and methods CBCT images of 142 individuals (72 women and 70 men) were classified according to the facial type (dolichocephalic, mesocephalic, or brachycephalic) and skeletal class (I, II, or III). The vertical and horizontal locations of each mental foramen were evaluated on panoramic reconstructions, and the greatest height and width of the mental foramen were determined on multiplanar reconstructions. Also, the distances from the mental foramen to the alveolar crest and to the inferior cortex of the mandible were obtained. The data were compared by using the Kruskal-Wallis test and multiway analysis of variance (α=.05). Results The facial type, skeletal class, and sex did not influence the vertical (P=1.00) or the horizontal (P>.15) location of the mental foramen. The most frequent location of the mental foramen was between the first and second premolars and below their apices. The dimensions of the mental foramen were not influenced by the studied factors in men (P>.07); conversely, the mental foramen dimensions were influenced for women (P Conclusions The most frequent location of the mental foramen was between the first and second premolars and below their apices. An influence of the facial type and skeletal class was observed on the dimensions of the mental foramen in women.

Neurofibromatosis (NF) is an inherited neuroectodermal abnormality that primarily affects the growth of neural tissues, and Riccardi classified it into eight types. Segmental neurofibromatosis, which is a rare form of neurofibromatosis, is classified as type 5. We report a case for very unusual presentation of segmental NF with unilateral lisch nodules and uncommon sites involving the scalp. Moreover, we could find only one case report of segmental NF with lisch nodules in the literature and could not find any case report involving the scalp.

Kidney disease is frequent in HIV-patients. We present a case of a 44-year-old woman, with known uncontrolled HIV infection and chronic kidney disease due to HIV-associated nephropathy. After starting dolutegravir, the patient developed eosinophilia and worsening kidney function. A kidney biopsy confirmed the diagnosis of acute interstitial nephritis. Given the time relation with dolutegravir introduction, it was deemed the culprit medication. Dolutegravir was stopped, and corticosteroids were initiated, with moderate improvement in renal function. To our knowledge, this is the first reported case of acute interstitial nephritis to dolutegravir, which should raise awareness of previously undocumented renal effects of antiretroviral therapy.

To determine the prevalence of abnormal laryngeal findings during videostroboscopy in performers presenting to clinic or when having an acute vocal emergency.Retrospective study of professional singers and actors who presented for a vocal evaluation.A chart review of singers or professional actors who presented in a private otorhinolaryngology clinic between 2014 and 2016. The prevalence of laryngeal lesions noted on stroboscopy were reviewed. The RFS (reflux finding score) was calculated and the exams that presented RFS greater than or equal to seven were considered suspicious of laryngopharyngeal reflux (LPR).A total of 140 records of actors and singers were evaluated either for routine evaluation or for an acute emergency. Sulcus vocalis was the most prevalent lesion 36% (n = 33), followed by cyst 27% (n = 25) and acute laryngitis, 14% (n = 13). Thirty-seven (26.4%) performers were treated for emergence due to dysphonia, Emergency dysphonia, mostly due to viral infection, was treated with steroids and speech therapy, with improvement of symptoms after treatment. Of these professionals, 83.8% (31) presented with a structural lesion or infection in the vocal folds, while 16.2% presented with dysphonia, which required emergency care without a structural lesion in the vocal folds. (P0.05) Eighty-nine percent (33) of the professionals presenting with a voice emergency with dysphonia (37) were treated with corticosteroids. Thirty-three percent (n = 47) of the professionals presented with RFS scores ≥7. Nineteen professionals (40%) with signs of LPR were treated for emergency due to dysphonia. The professionals with signs of LPR had more emergency dysphonia than those who did not suspect LPR. (19.4%) (P = 0.008).Vocal emergencies in professionals are common in a private laryngology practice and require specialized assessment. The most prevalent lesions in the study were vocal sulcus. LPR is common in this group as noted both by findings with videostroboscopy and the RFS.

Resumen Objetivo Este estudio fue disenado para determinar los predictores de la hipertension pulmonar y los signos de disfuncion cardiaca derecha causados por la embolia pulmonar (EP) que pueden conducir a la deteccion temprana de los pacientes de alto riesgo. Por lo tanto, se evaluo el valor predictivo del indice de obstruccion de la arteria pulmonar (IOAP), medido mediante angiografia pulmonar por TC (APTC) en el contexto agudo, para predecir los pacientes susceptibles de sufrir complicaciones cardiacas por EP. Tambien se investigaron otros dos indices de APTC, el diametro de la arteria pulmonar (DAP) y el strain del ventriculo derecho (VD), en estos pacientes y se demostro su valor predictivo de las complicaciones cardiacas en la ecocardiografia de seguimiento. Materiales y metodos En el estudio fueron incluidos 120 pacientes con diagnostico definitivo de EP. El IOAP, el DAP y el strain del VD se midieron mediante APTC en el momento del diagnostico inicial. Se realizo una ecocardiografia transtoracica 6 meses despues del diagnostico de EP y se midieron los indices ecocardiograficos del VD. Se utilizo la correlacion de Pearson para investigar la correlacion entre IOAP, DAP, strain del VD y los signos de disfuncion del hemicardio derecho. Resultados El IOAP estaba fuertemente correlacionado con la presion arterial pulmonar sistolica (PAPS) (r = 0,83), la presion sistolica del VD (r = 0,78) y el grosor de la pared del VD (r = 0,61) en la ecocardiografia de seguimiento a largo plazo. Se detecto una mayor tasa de disfuncion del VD y de dilatacion del VD entre los pacientes con mayor IOAP (p Conclusiones El IOAP, el DAP y el strain del VD son indices de APTC sensibles y especificos que pueden predecir el desarrollo de complicaciones a largo plazo, como la hipertension pulmonar y la disfuncion cardiaca derecha, en el momento del diagnostico inicial de la EP.

MiR-202-5p is identified as the maker microRNA (miRNA) of germplasm in fish. However, the role of miR-202-5p in gonadal development is still unclear. Here we investigated the expression patterns of miR-202-5p in Japanese flounder (Paralichthys olivaceus). Real-time PCR displayed that miR-202-5p was specifically expressed in bisexual gonads, and its transcription in the testis was relatively abundant than that in the ovary. Moreover, it was gradually increased in testis from stage II to stage IV. Fluorescent in situ hybridization (FISH) illustrated that miR-202-5p was co-localized with vasa (a marker gene of germ cells) in testis, and it was predominately expressed in spermatogonia and spermatocytes, implying that miR-202-5p might participate in spermatogenesis. Considering the important role of retinoic acid (RA) on regulating meiosis during spermatogenesis, we treated Japanese flounders by injecting all-trans retinoic acid (ATRA). MiR-202-5p in testis was shown to be up-regulated, and ccnd1, a key cell cycle regulator, was found to be down-regulated after ATRA treatment. Furthermore, ccnd1 was demonstrated to be a direct regulatory target of miR-202-5p using Dual-luciferase assay. In the primary testis cell from Japanese flounder, we further confirmed that ccnd1 was down-regulated by miR-202-5p. The results suggest that miR-202-5p exerts a crucial role in gonadal development by inhibiting ccnd1 in Japanese flounder.

A fetus with features of hydrops was given intra-uterine transfusion at 27 weeks and 31 weeks of gestation. Mother had been alloimmunized with anti-D and anti-C antibodies. At birth, laboratory investigations revealed bone marrow suppression along with features of hemolytic anemia. The neonate was started on a combination of phototherapy and intravenous immunoglobulin. During the course, the neonate was transfused with one unit of packed red cells (top-up transfusion). Neonatal hyperbilirubinemia responded to phototherapy and the bone marrow activity spontaneously resumed after 3 weeks of life. In neonates with anemia at birth who have history of multiple intra-uterine transfusions, early-onset hypoproliferative anemia should be considered.

Summary Objectives The understanding of vocal fold hydration state, including dehydrated, euhydrated, rehydrated tissue, and how hydration affects vocal fold biomechanical properties is still evolving. Although clinical observations support the benefits of increasing vocal fold hydration after dehydrating events, more mechanistic information on the effects of vocal fold dehydration and the beneficial effects of rehydration are needed. Alterations to hyaluronic acid (HA), an important component of the vocal fold extracellular matrix, are likely to influence the biomechanical properties of vocal folds. In this study, we investigated the influence of hydration state and HA on vocal fold tissue stiffness via biomechanical testing. Study design Prospective, ex vivo study design. Methods Fresh porcine vocal folds (N = 18) were examined following sequential immersion in hypertonic (dehydration) and isotonic solutions (rehydration). In a separate experiment, vocal folds were incubated in hyaluronidase (Hyal) to remove HA. Control tissues were not exposed to any challenges. A custom micromechanical system with a microforce sensing probe was used to measure the force-displacement response. Optical strain was calculated, and ultrasound imaging was used to measure tissue cross-sectional area to obtain stress-strain curves. Results Significant increases (P ≤ 0.05) were found in tangent moduli between dehydrated and rehydrated vocal folds at strains of e = 0.15. The tangent moduli of Hyal-digested tissues significantly increased at both e = 0.15 and 0.3 (P ≤ 0.05). Conclusion Vocal fold dehydration increased tissue stiffness and rehydration reduced the stiffness. Loss of HA increased vocal fold stiffness, suggesting a potential mechanical role for HA in euhydrated vocal folds.

PURPOSE To present a new technique to treat refractory retinal detachment secondary to optic disc pit. METHODS An interventional case report. RESULTS A 25-year-old man with congenital optic disc pit had two failed vitrectomies involving laser around the optic disc, internal limiting membrane peel and flap to plug the disc pit, and gas tamponade to reattach the retina. With all options running out, a further vitrectomy with autologous retinal transplant and silicone oil tamponade was carried out to treat the refractory serous retinal detachment; the silicone oil was removed at 6 weeks after the last procedure. The retina remained successfully attached at 6 months post-surgery with the patient maintaining his baseline visual acuity. CONCLUSION The use of autologous retinal transplant is a new approach to treat refractory retinal detachment secondary to congenital optic disc anomalies, and adds to our options of dealing with this complex condition when first-line approaches have failed.

Introduction Subtotal cholecystectomy (STC) is an alternative to total cholecystectomy (TC) in patients with severe inflammation/adhesions around the hepatocystic triangle. This study aimed to evaluate the safety profile of STC. Methods We retrospectively reviewed all patients who had STC at our unit between February 2009 and August 2019. STC was divided into two types, reconstituting (R-STC) and fenestrating (F-STC), depending on whether the gall bladder remnant was closed or left open. Patients who had cholecystectomy for gall bladder malignancy or as part of another operation were excluded from the study. Results A total of 5,664 patients underwent cholecystectomy during the study period. Of these, 97 (1.7%) underwent STC. The laparoscopic to open conversion rate was high at 48.8% (47 cases), as was the overall postoperative complication rate (45.4%, 44 cases). No patient suffered iatrogenic bile duct injury. Nineteen patients (19.6%) suffered postoperative bile leak. This was significantly higher in patients who had STC in the acute setting (41% vs 13% for elective STC cases; p=0.04). There was no significant difference in rate of bile leak or other complications between R-STC and F-STC types. The 90-day readmission rate was 8.2% (8 cases). No mortalities were recorded within 90 days post STC. Conclusions STC seems to be an effective technique to avoid bile duct injury in difficult cholecystectomy cases. However, the perioperative morbidity associated with STC is relatively high. Surgeons should be aware of the risks of STC and take appropriate steps to minimise them.

Purpose To describe central serous chorioretinopathy (CSCR) cases presenting as uveal effusion syndrome, providing new insights into "pachychoroid spectrum" diseases. Methods Clinical charts, color fundus photographs, fluorescein angiography, indocyanine green angiography, optical coherence tomography, ultrasound imaging, cerebral magnetic resonance imaging and biometry of four eyes of three patients were assessed. A literature review was conducted. Results The three patients had peripheral choroidal detachment and inferior bullous retinal detachment associated with CSCR features detected using multimodal imaging, including fluorescein and indocyanine green angiography. The choroid was thick in the three patients, and uveal effusion occurred after steroid treatment in all cases. Subretinal fluid drainage and deep sclerectomy with flaps of 4x4 mm in both inferior quadrants were performed in 3 eyes of 2 patients with good outcomes. One patient was treated with photodynamic therapy. All three patients developed a typical leopard-spot pigmentary pattern in the fundus. Conclusion A severe presentation of highly exudative CSCR may occur in rare cases with a peripheral choroidal detachment mimicking uveal effusion syndrome. These severe cases highlighted the role of choroidal thickening and hyperpermeability, choroidal vein dilation and possible scleral thickening in both entities.

Malakoplakia is a rare granulomatous inflammatory disorder. Its diagnosis depends on histopathological findings; however, high-quality literature regarding proper medical/surgical treatment is lacking. A 38-year-old diabetic female patient was admitted to the emergency room with a history of lower gastrointestinal hemorrhage. Colonoscopy revealed a lesion in the descending colon, and abdominal computed tomography revealed a splenic flexure mass involving the lower pole of the spleen and upper pole of the left kidney. Biopsies confirmed the diagnosis of malakoplakia. After completing antibiotic treatment, a restaging computed tomography revealed a discrete mass increase; hence, the patient underwent laparoscopic en bloc colectomy and partial nephrectomy. Postoperatively, the patient developed a pancreatic fistula, which was successfully treated with percutaneous drainage and antibiotics. The presence of pathognomonic Michaelis-Gutmann inclusions on histopathology is frequently reported as the key to diagnosing malakoplakia. Herein, we present a successful, minimally invasive surgical treatment for colonic malakoplakia.

An Amyand’s hernia is characterised as the presence of the appendix in an inguinal hernial sac. During laparoscopic cholecystectomy for gallbladder polyps, an incidental Amyand’s hernia was discovered in a 75-year-old female patient. On examination, the hernia contained an appendiceal mucocele but no evidence of perforation. An open appendicectomy with tension-free mesh repair was performed for the hernia. The histopathological report of the appendix was a low-grade appendiceal mucinous neoplasm (LAMN), an entity that is just as rare as an Amyand’s hernia. The patient had the right inguinal swelling for over 10 years but it was thought to be an inguinal intramuscular cyst as reported on a previous abdominal ultrasound. Mucocele of the appendix may have a benign or malignant appendiceal progress, leading to individualised diagnosis and treatment. We review an Amyand’s hernia with LAMN and discuss the asymptomatic tendency yet malignant potential of appendiceal mucoceles along with treatment strategies.

Background: Cardiac amyloidosis (CA), following a non-invasive diagnosis, constitutes an increasingly prevalent heart failure (HF) etiology. This study aims to determine which echocardiography findings help to diagnose cardiac amyloidosis in patients with left ventricular hypertrophy (LVH) admitted for decompensated HF. M ethods: The present study is a retrospective observational study on a cohort of 85 LVH patients admitted for HF decompensation, in which 99m Tc-DPD scanning was performed to rule out transthyretin CA. The echocardiographic findings obtained were compared between CA and non-CA groups. Results: From a total number of 85 patients, 49 (57.6%) met the CA criteria and 36 (42.3%) were ruled out for the disease. Interventricular septum thickness (16 ± 3 mm vs. 14 ± 3 mm), left ventricular posterior wall thickness (14 ± 3 mm vs. 11 ± 2 mm), left ventricular mass (259 ± 76 g vs. 224 ± 53 g), left ventricular telediastolic diameter (48 ± 7 mm vs. 53 ± 6 mm), left ventricular telediastolic indexed volume (51 ± 18 cm 3 /m 2 vs. 59 ± 16 cm 3 /m 2 ), tricuspid annular plane systolic excursion (16 ± 5 mm vs. 20 ± 4 mm), right atrial area (27.4 ± 8.4 cm 2 vs. 22.2 ± 5.7 cm 2 ) and strain relative apical sparing (2.2 ± 0.9 vs. 1.03 ± 0.4; p = 0.04) were significantly associated with the diagnosis of CA. Conclusions: In patients with LVH admitted for HF decompensation, there are several echocardiographic features (LVH, reduced left ventricular cavity size, strain relative apical sparing, right atrial dilation, and altered right ventricular function) that are associated with the diagnosis of cardiac amyloidosis.

The aim of this study was to analyse the vertical location of the posterior superior alveolar artery (PSAA) using a reliable new reference plane regardless of tooth and alveolar bone, and to measure the diameter in each posterior tooth region, which is of relevance to lateral sinus floor elevation surgery. A total of 270 sinuses in 139 patients were examined in this study. The A-plane was defined by A-point and the bilateral jugal points on reconstructed three-dimensional images. The distance from the PSAA to the defined plane was measured in four regions: first premolar (P1), second premolar (P2), first molar (M1), and second molar (M2). The average distance of the PSAA above the plane in the P1, P2, M1, and M2 regions was determined to be 10.24mm, 7.35mm, 5.47mm, and 7.23mm, respectively. The PSAA was found to run above the plane in 97.4% of sinuses, below the plane in 1.1%, and on the plane in 1.5%. In conclusion, the new plane is useful for intraoperative location of the PSAA. According to the study findings, the area below the reference plane can be considered safe for lateral approach sinus surgery in terms of preserving the integrity of the PSAA.

This work explores an efficient integration of IoT devices based on context awareness in the agricultural sector. A four-layered framework is proposed in which automation techniques are embedded to get real-time context aware insights from the ecosystem of IoT. The framework is evaluated using a strategic tool called threats, opportunities, weaknesses and strengths (TOWS) matrix to measure the performance of automation techniques. This analysis points out various opportunities to innovate the livelihood of agrarian society around the globe.

Research on the quantification of 3-dimensional tooth movements in patients undergoing treatment using the Dahl principle is lacking.The purpose of this observational clinical study was to measure the magnitude, direction, duration, and rate of tooth movement occurring in patients to reestablish tooth contact and create restorative space.A total of 104 paired preoperative and postoperative physical and virtual casts from 26 patients were obtained. Commencement and completion dates were recorded to calculate movement duration to reestablish occlusion. Dental casts were digitized, and the 3-dimensional digital casts obtained were superimposed via a surface matching and analysis software program by using the global registration function. Color maps were used to visualize direction, and the annotation feature quantified magnitude of tooth movement in millimeters when specific reference points were selected. Teeth within the arch were categorized as per their location to evaluate their impact on occlusal reestablishment. The average rate of movement was determined by time taken for extrusive and intrusive movements over the treatment duration. Post hoc Tukey tests were applied if a significant difference was present in the magnitude of movement between different tooth categories.All participants showed evidence of tooth movement during treatment. Duration of occlusal reestablishment ranged from 3.9 to 28.2 months, with more posterior tooth extrusive movements (56.9%) than anterior tooth intrusive (43.1%) movements occurring. A comparison of magnitude of extrusive or intrusive movement between categories (molar-anterior, premolar-anterior, and premolar-molar) showed that premolar and molar extrusive movements and anterior intrusive movements were significantly different (P.001). The amount of buccal and lingual movement for molars and premolars was similar. Anterior teeth demonstrated more buccal than lingual movements. All teeth showed more mesial than distal movements. The extrusive and intrusive movement rate was 0.13 and 0.11 mm/mo, respectively.Tooth movement occurred in patients regardless of age and sex. The results of this study indicated that tooth movements have a 3-dimensional nature. Occlusal reestablishment mainly occurred via a combination of extrusive and intrusive movements. The study further highlighted the advantages of digital technology such as surface scanners and 3-dimensional software programs that can be used to quantify change in patients undergoing treatment.

Objective To characterize the multimodal retinal findings of myopic macular pits, a feature of myopic degeneration. Methods A case series of patients with myopic macular pits were studied with multimodal imaging including color fundus photography, fundus autofluorescence (FAF), near infrared reflectance (NIR), spectral domain optical coherence tomography (OCT), optical coherence tomography angiography (OCTA), fluorescein angiography (FA) and indocyanine green angiography (ICG). Results Nine eyes of 6 patients with myopic macular pit were examined. Four patients presented with multiple pits and 3 with bilateral involvement. All pits were localized in a region of severe macular chorioretinal atrophy associated with myopic posterior staphyloma. In 3 eyes, the entrance of the posterior ciliary artery through the sclera was noted at the base of the pit. Schisis overlying the pit or adjacent to the pit was identified in 3 patients. Conclusion Myopic macular pits are an additional rare sign of myopic degeneration, developing in regions of posterior staphyloma complicated by severe chorioretinal atrophy and thin sclera.

Objective To evaluate the long-term structural and microvascular retinal effects of internal limiting membrane peeling for full-thickness macular hole (FTMH) using en face adaptive optics optical coherence tomography (AO-OCT), conventional OCT, and OCT angiography (OCTA). Design Interventional case series. Participants Patients with FTMH treated with vitrectomy, internal limiting membrane peeling, and gas tamponade. Methods Eleven eyes with FTMH that had at least 12 months of postoperative follow-up were enrolled in the study. En face AO-OCT was used to image the superficial retina in the peeled and nonpeeled areas. En face structural OCT was performed to image the inner retinal dimples (IRDs), macular thickness, and retinal nerve fibre layer (RNFL). En face OCTA was used to examine the integrity of the peripapillary nerve fibre layer (NFL) plexus. Results AO-OCT showed RFNL wrapping around the IRDs, and no obvious peripapillary NFL plexus dropout was seen with OCTA. Scattered hyper-reflective dots were observed on the surface of the peeled retina in all patients imaged with AO-OCT. No significant differences were found in IRD number (91.5 ± 24.4 versus 77.2 ± 14.7; P = 2.07), IRD proportionate area (8.36 ± 3.34 versus 7.53 ± 2.60; P = 0.159), or macular thickness between the 6- and 12-month (or greater) postoperative visits. Conclusion IRDs do not to progress beyond 6 months postoperatively, and no obvious damage to RFNL and peripapillary NFL plexus was detected. Hyper-reflective dots on the surface of the retina suggestive of possible Muller cell reactive gliosis were identified with AO-OCT.

Objective This study aimed to analyze our outcomes of primary premaxillary ostectomy and setback combined with lip adhesion as the first stage in repair of the bilateral cleft lip with fly-away premaxilla. Methods This retrospective study included all patients who required primary premaxillary setback by a single surgeon to achieve successful lip repair between 2011 and 2017 at a tertiary children's hospital. All patients had bilateral cleft lip and complete cleft palate with significant premaxillary protrusion. All patients either had failed presurgical orthodontic manipulation or were thought to be poor candidates because of the rigidity of the premaxilla on clinical examination. Patient data were obtained from review of medical records and photographs. Surgical technique is described. Results Eleven patients with bilateral cleft lip, all of whom also had complete cleft palate, underwent primary premaxillary setback and lip adhesion at an average age of 8.2 months. The mean follow-up was 1.9 years (range, 139 days to 4.5 years). All patients subsequently completed formal lip repair, of which 10 have undergone palatoplasty. Serial photography documented stable premaxillary position and successful lip repair within the follow-up time frame. No patient had postoperative premaxillary instability or vascular compromise. One patient had dehiscence of the lip adhesion requiring reoperation. Conclusions Primary premaxillary ostectomy and setback allows for successful staged formal lip repair in patients with bilateral cleft lip and palate who have failed presurgical infant orthopedics. Further research is required regarding long-term follow-up with respect to midfacial growth.